Virology molecular biology and pathogenesis

Tai Lieu Chat Luong VIROLOGY MOLECULAR BIOLOGY AND PATHOGENESIS This page intentionally left blank V ROLOGY MOLECULAR BIOLOGY AND PATHOGENESIS LEONARD C NORKIN Department of Microbiology University of Massachusetts Amherst, Massachusetts ASM PRESS Washington, DC Address editorial correspondence to ASM Press, 1752 N St NW, Washington, DC 20036-2904, USA Send orders to: ASM Press, P.O Box 605, Herndon, VA 20172, USA Phone: (800) 546-2416 or (703) 661-1593 Fax: (703) 661-1501 E-mail: books@asmusa.org Online: http://estore.asm.org Copyright © 2010 ASM Press American Society for Microbiology 1752 N St NW Washington, DC 20036-2904 Library of Congress Cataloging-in-Publication Data Norkin, Leonard C Virology : molecular biology and pathogenesis / Leonard C Norkin p ; cm Includes bibliographical references and index ISBN 978-1-55581-453-3 (hardcover : alk paper)  1.  Virology—Textbooks 2.  Molecular virology—Textbooks 3.  Virus diseases— Pathogenesis—Textbooks.  I.  Title [DNLM: 1.  Viruses—pathogenicity 2.  Genome, Viral 3.  Virus Diseases—etiology 4.  Viruses—genetics.  QW 160 N841v 2010] QR360.N67 2010 616.9′101—dc22 2009036895 10  9  8  7  6  5  4  3  2  All rights reserved Printed in Canada Cover and interior design: Susan Brown Schmidler Illustrations: Lineworks, Inc Cover illustration: Structure and molecular organization of a Sindbis virus particle Sindbis virus is a member of the togavirus family of enveloped plus-strand RNA viruses The surface features of the particle were determined by cryo-electron microscopy, which yielded hundreds of highly detailed, two-dimensional images, from which a three-dimensional image was generated using powerful computer programs A cross-section through the particle, showing the envelope glycoproteins (blue), the lipid bilayer (green), the nucleocapsid (red), the mixed RNA-protein region (orange), and the genomic plus-strand RNA (magenta), is superimposed on the three-dimensional image Protein structures were solved by X-ray crystallography, and then fitted into the cryo-EM structure See Figure 8.1 in the book for the complete image Adapted from W Zhang et al., J Virol 76:11645–11648, 2002, with permission I dedicate this book to my wife, Arline; my sons, Dave and Mike, and their wives, Mina and Debbie; and my grandchildren, Luke, Maya, and Theo ‘‘Human subtlety will never devise an invention more beautiful, more simple or more direct than does Nature, because in her inventions, nothing is lacking and nothing is superfluous.’’ Leonardo da Vinci (1452–1519) This page intentionally left blank Contents Preface xix PART I  Introduction 1 A Selective History on the Nature of Viruses Introduction The Early Years: Discoverers and Pioneers The First Stirrings of the Molecular Era The Phage Group 10 Phage Growth: Eclipse and Replication 11 Defining Viruses 15 Are Viruses Alive? 16 Origin of Viruses 17 The Modern Era of Animal Virology 17 2 Biosynthesis of Viruses: an Introduction to Virus Classification 20 T-Even Bacteriophages as a Model System 20 T-Even Phage Structure and Entry 22 Sequence of Phage Biosynthetic Events 24 Phage Protein Synthesis 24 RNA Metabolism in Infected Cells 25 Assembly of Progeny Phages 27 Packaging DNA within the Phage Particle 28 Unique Features of T-Even Phages 30 Modified Bases 30 Regulated Gene Expression 30 Phage Release: Lysozyme and the rII Region 32 Bacteriophage Lambda (λ): Lysogeny and Transduction 33 Some Final Comments on Bacteriophages 39 vii viii CONTENT S Introduction to the Animal Viruses 39 Animal Virus Structure 39 Entry of Animal Viruses 42 The Families of Animal Viruses: Principles of Classification 45 Viral Genetic Systems: the Baltimore Classification Scheme 45 Modes of Virus Infection and Disease 50 Introduction 50 Portals of Entry 50 Routes of Dissemination 54 Hematogenous and Neural Dissemination 54 The Placenta and the Fetus 60 Acute versus Persistent Infections 63 Acute Infections 64 Persistent Infections 66 Slow Infections 66 Chronic Infections 68 Latent Infections 74 Transmissible Spongiform Encephalopathies: Prions 76 Host Defenses and Viral Countermeasures 80 Introduction 80 Overview of Defenses 81 Physical Barriers against Infection 82 The Innate Immune System 82 Cytokines: the IFNs 84 Cytokines: TNF-α, Some Other Cytokines, and Inflammation 88 Macrophages, Neutrophils, NK Cells, and Antibody-Dependent Cellular Cytotoxicity 89 The Complement System 95 Viral Evasion of Innate Immunity 98 Evasion of IFNs 98 Evasion of Cytokines 100 Evasion of NK Cells and ADCC 101 Evasion of Complement 102 APOBEC3G and the HIV Vif Protein 103 The Adaptive Immune System 103 Antibodies and B Cells 104 Antibody Diversity 106 Viral Evasion of Antibodies 110 Cell-Mediated Immunity 113 Antigen Presentation by MHC Class I Molecules 119 Antigen Presentation by MHC Class II Molecules 119 The Rationale for MHC Restriction 121 Activation of Th Cells: Dendritic Cells and B Cells 124 Activation of B Cells 126 Activation of CTLs 128 Mechanism of Action of CTLs 129 CONTENTS T Cells and Antiviral Cytokines 131 Viral Evasion of Cell-Mediated Immunity 132 Inhibition of Antigen Presentation to CTLs 132 Inhibition of Antigen Presentation to Helper T Cells 134 Inhibition of Apoptosis 134 Immunological Memory 136 Self Tolerance 137 The Immune System in Disease 140 Immunopathology 140 Autoimmune Disease 141 PART II  Virus Replication and Pathogenesis 147 RNA Viruses: Double Stranded 149 Reoviruses 149 Introduction 149 Structure, Binding, Entry, and Uncoating 150 Reovirus Binding and Entry into the Cell 150 Structure, Uncoating, and Entry into the Cytoplasm 154 The Reovirus Genome: Transcription and Translation 156 The Particle-Associated RNA Polymerase 156 The Segmented Reovirus Genome 158 Conversion of ISVPs to Cores 161 Replication and Encapsidation of the Reovirus Genome 165 Synthesis of Double-Stranded RNA 165 Assembly of Progeny Subviral Particles and Encapsidation of RNA Segments 166 Reoviruses and IFN 166 Primary versus Secondary Transcription 167 Final Virus Assembly 168 Pathogenesis 168 Orthoreoviruses 168 Rotaviruses 168 Coltiviruses 169 RNA Viruses: Single Stranded 171 Picornaviruses 171 Introduction 171 Structure, Binding, and Entry 172 Picornavirus Structure 172 Rhinovirus Receptor and Binding: the Canyon Hypothesis 173 The Poliovirus Receptor 177 Receptors for Coxsackieviruses and Other Enteroviruses 179 Receptors for FMDVs 180 Poliovirus and Rhinovirus Entry: Some General Points 181 Poliovirus Entry 181 ix 712 IND E X Meitner, Lise, 10, 11 MEK (MAP kinase kinase), 580, 581 Membrane attack complex (MAC), 95–96 Membrane fusion coronavirus entry and, 237–238, 239 hemifusion, 633 hemifusion intermediate, 306, 307 HIV entry and, 611, 615, 616, 617 models for, 239 orthomyxoviruses, 302–307 retrovirus entry and, 561–562 SNARE proteins, 303–304, 306, 307 transition states in, 306 vaccinia virus entry by, 527–529 Membrane (M) protein of coronaviruses, 236–237, 251 Membrane permeabilization, adenovirus and, 451 Membrane-remodeling activities, virus-encoded, 194–195 Memory B cells Epstein-Barr virus (EBV) infection of, 509 Epstein-Barr virus (EBV) latency in, 499–503 Memory T cells HIV infection of, 623 HIV latency in, 635 Menangle virus, 294 Meninges, 57, 60 Meningitis echovirus, 172 herpes simplex virus (HSV), 508 mumps virus, 290 symptoms, 205 Meningoencephalitis, 213 Merkel cell carcinoma, 379, 417–418 Meselson, Matthew, 25, 26–27 Messenger RNA (mRNA) See also Transcription; Translation capping (See Capping) monocistronic, 192 nested set of coronavirus, 235, 242 nuclear export of, 321 nuclear transcription of bornavirus, 354 polycistronic, 188, 192 Shine-Dalgarno sequences, 192 splicing (See Splicing) subgenomic, togavirus, 229, 231 translation initiation sites, 160 Metastable conformation, 29 MHC molecules allotype, 113, 123 antigen presentation by MHC I molecules, 119, 120 by MHC II molecules, 119, 121, 122, 543 inhibition of CTLs, 132–134 inhibition of Th cells, 134 classes, 115 gene polymorphism, 113, 114, 117 isoform, 114, 117 MHC-I molecules, 92 adenovirus interference with, 465 as adenovirus receptors, 448–449 herpes simplex virus (HSV-1) suppression of, 496, 497 HIV Nef protein down-regulation of, 622, 625, 635 human cytomegalovirus (HCMV) impairment of, 504–505 molluscum contagiosum virus homologs of, 542, 543 polymorphism and HIV disease progression, 625 shedding of, 382 SV40 binding to, 382 viral evasion of host immunity and, 102 MHC-II molecules as Epstein-Barr virus (EBV) entry receptors, 479, 503 HIV Nef protein downregulation of, 635, 636 human cytomegalovirus (HCMV) impairment of, 504, 505 low expression by anergic T cells, 634 vaccinia virus interference with, 543 structure of, 115–118 MHC restriction, 113, 114, 121–124 MHV (mouse hepatitis virus), 235, 238, 239, 241, 242, 245, 250 MIBE (measles inclusion body encephalitis), 285 Microtubule-associated fast axonal transport, 55–56 Microtubules adenovirus transport, 451 orthomyxovirus transport, 301 poxvirus assembly and exit, 536–537 Mimivirus, 17, 524 Minichromosome hepadnavirus, 678, 680 polyomavirus genome as, 380, 384–386 Minus-sense RNA viruses bornaviruses, 352–355 bunyaviruses, 350–352 filoviruses, 358–361 orthomyxoviruses, 296–345 paramyxoviruses, 273–295 plus-strand RNA viruses compared, 184 rhabdoviruses, 261–272 Minute virus of mice (MVM), 367, 368, 369, 374 MIP-1a, 90, 611 MIP-1b, 611 miRNA, SV40 and, 413–414 Missense mutation, 189 Mitochondrial permeability transition pore blockage by poxviruses, 541, 542 role in intrinsic apoptosis pathway, 541, 542 Mitogen-activated protein (MAP) kinases, 405–406, 408, 580, 581, 582, 584 Mizutani, Satoshi, 558 MLV See Murine leukemia virus (MLV) MMR vaccine, 234, 285, 289–290, 290, 291 MMRV vaccine, 234 MnK1, 459 Modified bases, of T-even phages, 30 Molecular Biology of the Gene (Watson), 380 Molecular chaperones cochaperones, 162 description, 162 reovirus capsid disassembly, role in, 162 Molecular mimicry, 142–143 Molluscum contagiosum virus (MCV) clinical presentation, 544–546 clinical syndromes, 523, 544–546 evasion of cytokines, 100–101 evasion of NK cells, 102 impairment of CTL-mediated immune defenses, 542 skin tumors from, 546 Moloney murine leukemia virus, 592 Monoclonal antibodies for identification of receptors, 151 poliovirus receptor identification by, 177 rhinovirus receptor identification by, 175 Mononegavirales, 262, 265, 267, 273, 296, 346, 352 Mononegaviruses, gene organization and transcription in, 264–267 Mononuclear phagocyte system, 58 Mononucleosis cytomegalovirus, 473 EBV (Epstein-Barr virus), 473, 508, 509 Monopartite minus-strand RNA genome, 262 Montagnier, Luc, 556, 602, 603–605, 658 Moore, Patrick, 515 Morbillivirus, 274, 275 Morgan, Doris, 602 Mosquito vectors for encephalitic alphaviruses, 232 Motor protein, 301 Mouse hepatitis virus (MHV), 235, 238, 239, 241, 242, 245, 250 See also Coronaviruses Mouse mammary tumor virus, 553, 554, 579 M-PMV (Mason-Pfizer monkey virus), 575 M protein See Matrix (M) protein mRNA See Messenger RNA (mRNA) MS See Multiple sclerosis MS2 bacteriophage, 187, 188, 190–191 Mucosa alimentary tract, 52 apical versus basal release of virus, 57–58 barriers to infection, 82 polarization of cells, 57 respiratory, 51 small intestine, 52 Muerto Canyon virus, 351 Mullis, Kary, 666 Multipartite minus-strand RNA genome, 262 Multiple sclerosis, 143–145, 172, 286 human herpesvirus (HHV-6) link to, 514 natalizumab therapy for, 416–417 Multivesicular body (MVB), 263, 622–623 Mumps, 290 INDE X Mu phage, 38 Murine leukemia virus (MLV) as oncogene-deficient oncogenic retrovirus, 577 as oncornavirus, 554 assembly, 575 nuclear entry and integration, 567 packaging signals, 575 translational read-through strategy, 572 Murine mammary tumor virus, 553, 554, 579 Mutation amber (chain-terminating), 32, 189 conditionally defective, 32 immune escape mutants, 111 minimal unit of, 34 pseudorevertants, 400 somatic hypermutation, 103, 109, 595 temperature sensitive, 32 MVB (multivesicular body), 263, 622–623 MVM (minute virus of mice), 367, 368, 369, 374 myc gene, 585, 589–590 Mycobacterium avium complex (MAC), 644 Mycobacterium tuberculosis, 216, 599, 644–645 Myc protein, 406 Myelitis, 56–57 Myelopathy, human T-cell leukemia virus (HTLV-1)-associated, 667 Myocarditis from coxsackie B virus, 172 Myristoyl group, 156 Myxomas, 542 Myxomatosis, 539 Myxoma virus antiapoptotic Ml 1L protein, 542 CrMA protein of, 540–541 degradation of MHC-1 molecules and, 542 evasion of cytokines, 100 evasion of interferons, 98 inhibition of PKR by, 539 M-T7 protein as anti-inflammatory therapeutic agent, 540 viroceptor for interferon, 539 Myxoviridae, 297 Myxoviruses, 274 N NA See Neuraminidase (NA) N-Acetyl-9-O-acetylneuraminic acid as receptor for coronavirus, 238 Namibia, AIDS in, 662 Nasopharyngeal carcinoma, 509, 510–511 Natalizumab (Tysabri), 415, 416–417 Natural killer (NK) cells functions of, 91–95 human cytomegalovirus (HCMV) blockage of, 505 inhibition by poxviruses, 540 interferon and, 87, 88, 90, 91, 92 macrophage activation by, 90 receptors, 89, 92, 93 resting, 92 viral evasion of, 101–102 NC protein See Nucleocapsid protein Necrosis, 130 Nectins as herpesvirus entry receptors, 476–478 Needle exchange programs, 656–657, 659 Nef protein, HIV, 601, 617, 622, 632, 635–636 Negative noodles, 486 Neonatal infections herpes simplex virus (HSV), 507, 508 human cytomegalovirus (HCMV), 512–513 HIV, 607, 614 Neonatal tolerance, 141 Neoplasia adenoviruses and, 446, 456–457 antiangiogenic approach to therapy, 468–469 carcinomas, 646 cervical carcinoma, 73, 433–442 historical information, 421 incidence, 419–420 molecular mechanisms, 433–439 stages of cancer development, 439 tissue microenvironment, 439–440 Epstein-Barr virus (EBV)-associated, 509–511 gene therapy, 467–469 hepatocellular carcinoma, 221, 673, 688–689 human herpesvirus (HHV-8)associated, 515–516 in AIDS patients, 644, 645–646 oncornaviruses and, 553, 554 oropharyngeal, 442–443 penile, 433 p53 mutations and, 467 polymavirus and, 378, 379, 401–410 sarcomas, 646 spontaneous, 579 targeted therapy approach, 468 viral etiology of, 422 Neoplastic transformation by adenoviruses, 456–458, 459 by polyomavirus, 378, 401–410, 459 by SV40, 401–410 differences between normal and transformed cells, 379 hit-and-run hypothesis/mechanism, 402, 459 permissive cells, 401–402 susceptible cells, 401 Temin’s quantitative assay for, 557 Nephropathy, polyomavirus, 415 NEP (nuclear export protein) of influenza virus, 298–299, 322–323 Nervous system blood-brain barrier description, 57, 60, 112–113, 216 HIV effect on, 415 brain blood-brain barrier, 57, 60, 112–113, 216, 415 as immunologically privileged site, 112 rabies virus infection of, 270–271 713 central nervous system disease dementia, AIDS-related, 646–647 measles virus complications, 284–288 mumps, 290 progressive multifocal leukoence­ phalopathy (PML), 378, 410, 414–417 dissemination of virus in, 55–57 invasion from blood circulation, 59–60 neuronal transport, 55–56 neurons herpesvirus infection of, 476, 494–496, 498 rabies virus infection of, 270–271 neurotropic viruses, 55, 153 Neural dissemination, 55–57 Neuralgia, postherpetic, 513 Neuraminidase (NA) influenza virus, 298, 299, 332, 334 paramyxoviruses, 275 Neuroinvasive, 57 Neuronal transport, 55–56 Neurons herpesvirus infection of, 476, 494–496, 498 neuronal transport, 55–56 rabies virus infection of, 270–271 Neuropsychiatric disease, Borna disease virus and, 352–354 Neurotropic viruses, 55, 113, 153 Neurovirulent, 57 Neutralization, complement and, 95 Neutralizing antibodies mechanism of action, 82, 217 shortcoming of, 104 to adenovirus, 444 to HIV, 616, 624 to influenza virus, 337 to rhinoviruses, 176, 177 Neutrophils diapedesis, 89 inflammatory response, 88 innate immune system and, 90–91 Nevirapine, 649 NF-κB activation by HIV Nef protein, 635 activation by HIV Vpr protein, 638 activation by human T-cell leukemia virus (HTLV-1) Tax protein, 668 HIV requirement for, 618–619 inhibition by IκB, 618–619 inhibition by poxviruses, 540, 541 Nf-1 transcription factor, 460 Nibert, M.L., 154 Nicotinic acetylcholine receptors, rabies virus binding to, 270 Nipah virus, 273, 279, 294–295 Nirovirus genus, 350 Nitric oxide (NO), 87–88 Nitric oxide synthetase (NOS2), 87 NK cells See Natural killer (NK) cells Nocodazole, 301 Nonessential genes of herpes simplex virus (HSV-1), 484 NO (nitric oxide), 87–88 714 IND E X Non-LTR retrotransposons, 593 Non-nucleoside reverse transcriptase inhibitors for HIV, 626, 648, 649 Nonprogressors, HIV, 217 Nonreceptor protein-tyrosine kinase, 580, 582, 588 Nonsense mutation, 189 Norovirus, 355–356 Norwalk virus, 347, 355–356 NOS2 (nitric oxide synthetase 2), 87 Notch-1, 406 NP protein See Nucleocapsid protein N protein See Nucleocapsid protein Nuclear export of bornavirus, 355 of cellular mRNAs blockage by influenza virus NS1 protein, 320–321 TAP/NXF and, 323 of HIV RNAs, 323 of HIV transcripts, 620–621 of influenza virus vRNPs, 322–323 Nuclear export protein (NEP) of influenza virus, 298–299, 322–323 Nuclear export signal description of, 309 exportins and, 321 Rev, 621 Nuclear lamina, 400–401 Nuclear localization signals astrovirus, 357 bornavirus, 355 cytoplasmic receptors, 310 influenza virus, 308, 309–311, 322 length of, 309 of SV40 LT antigen, 400 on nucleocapsid (NP) protein, 311 parvovirus and, 365 Nuclear pore complexes adenovirus interaction with, 451–452 description of, 309–311 herpesvirus entry across, 480–481 Nucleic acid testing for HIV, 660–661 Nucleocapsid protein coronavirus, 236–237, 251 influenza virus, 297, 299, 300, 311, 317–318 nuclear localization signals on, 311 paramyxovirus, 274, 279, 281 retrovirus, 559–560, 574, 575, 576 rhabdovirus, 262, 265–269 Nucleoside/nucleotide analogs HIV, 647–648, 649, 650 structure of, 518 Nucleosomes of SV40 minichromosome, 385–386 Nucleus adenovirus assembly in, 462 adenovirus entry into, 452 bornavirus replication in, 354–355 hepadnavirus entry and release, 676 hepatitis D virus transcription and replication in, 693 herpesvirus assembly and release from, 488–493 herpesvirus entry into, 480 orthomyxovirus transcription in, 317 transport of orthomyxovirus ribonucleoprotein segments to, 308–311 Nude mice, 94 O Octamer-binding protein (Oct1) herpesvirus, 460, 485–486, 496 Ocular disease, adenovirus, 466 OHL (oral hairy leukoplakia), 512 2′-5′-Oligoadenylate synthetase activation by double-stranded RNA, 319 herpes simplex virus (HSV-1) impairment of, 497–498 inhibition by vaccinia virus, 539 interferon induction of, 87, 538 Oligodendrocytes, 72 onc gene retrovirus, 564, 569 Oncogene-deficient oncogenic retroviruses, 588–591 Oncogenes abl, 582 cellular, 578–580 erbA, 585 erbB, 582, 588 functional classes of oncogenes transduced by retroviruses, 583–584 myc, 585, 589–590 onc, 564, 569 proto-oncogenes, 579–580, 582, 588–591 raf, 585 ras, 579, 580, 584 simple retroviruses, 554 sis, 582 src, 577–578, 580, 582 viral, 459 Oncogenesis insertional activation, 588–591 retroviruses and, 576–591 oncogene-deficient oncogenic retroviruses, 588–591 oncogene-transducing oncogenic retroviruses, 577–588 Oncogenic viruses, 422 Oncoproteins, 437 See also specific oncoproteins sites of action of, 582 table of, 583–584 Oncornaviruses, 553, 554 See also Retroviruses One gene-one mRNA-one protein hypothesis, 27 One gene-one ribosome-one protein hypothesis, 27 One-step growth experiment, 11–13 Operators, 35–37 Opportunistic infections, AIDS and, 643–645 Opsonization, 95 by antibody, 88, 90, 97–98 by complement, 97–98 Oral cavity, as portal of entry, 52 Oral hairy leukoplakia (OHL), 512 Oral infection, herpes simplex virus (HSV), 507–508 Orbiviruses, 149–150 Orchitis, mumps viral infection and, 290 Organism, definition of, 17 Organotypic raft culture, 424 Origin of replication herpesvirus, 481, 501, 502 papillomavirus, 429 polyomavirus, 388–390, 395 Origin of viruses, 17 Ornithine transcarbamylase, 467 Oropharyngeal cancer, 442–443 Orphan virus, 515 Orthomyxoviridae, 296–297 Orthomyxoviruses, 296–345 assembly, 322–325 classification, 296–298 entry, 299–311 endocytosis, 300–302 genome release from envelope, 307–308 intracellular trafficking of endosomes, 301–302 membrane fusion, 302–307 M2 protein, role of, 307–308 overview of, 299–300 transport of viral ribonucleoprotein segments to nucleus, 308–311 genome organization and transcription, 311–317 host range, 297 innate host defenses, evasion of, 318–322 medical aspects, 325–344 antigenic drift and antigenic shift, 328–334 anti-influenza virus drugs, 336–337 avian influenza virus, 337, 339–344 pandemic of 1918, 326–328 pathology and clinical syndromes, 325–326 vaccine, 298, 337, 338–339, 343–344 virulence of 1918 pandemic influenza virus, 334–336 overview, 296–298 paramyxoviruses compared, 274 release, 325 replication, 317–318 structure, 298–299 switchover from transcription to replication, 317–318 Orthoreoviruses, 149–150, 168 See also Reovirus Oseltamivir, 325, 336, 342, 344 Osmotic shock, release of DNA from phage by, 13, 14 Otitis media, measles virus and, 284 P p21, 406, 458 p23, 450–452 p27, 406 p53 activation by DNA damage, 136 apoptosis and, 136, 403 INDE X as tumor suppressor protein, 136, 576 caspase activation by, 136 cell cycle arrest and, 403 inactivation by adenovirus E1A protein, 458 by adenovirus E1B protein, 457, 458 by hepadnaviruses, 687, 688 by papillomaviruses, 434–435, 437–439 SV40 LT antigen interaction with, 379, 402–404 p107, 402 p130, 402 PABP (poly(A)-binding protein), 193, 196, 198 Packaging signal adenovirus, 463–464 coronavirus, 251 retrovirus, 575 PACT, 497, 498 Pactamycin, 185 Palindromic sequences in parvovirus genome, 365–367, 371 Palm civets as SARS source, 256–257 Panama Canal, yellow fever and, 219 Pandemic, influenza, 141, 298, 326–328, 334–336, 599 Papillomas, 420 Papillomaviridae, 378, 404, 407, 419, 422 Papillomaviruses, 419–443 cervical carcinoma, 433–442 molecular mechanisms, 433–439 stages of cancer development, 439 tissue microenvironment, 439–440 chronic infections, 73 entry and uncoating, 421–424 genome organization and expression, 424–429 historical information, 421 oropharyngeal cancer, 442–443 oropharynx as entry site for, 52 raft cultures, 424 release and transmission, 432–433 replication, 429–432 in skin, 51 structure, 420–421 treatment and prevention, 441–442 vaccine, human papillomavirus (HPV), 441–442, 443 Papovaviridae, 378, 419 Pap smear, 440, 442 Parainfluenza virus, 278, 290 Paramyxoviridae, 273 Paramyxovirus, 274, 275 Paramyxoviruses, 273–295 assembly and release, 282 entry, 275–279 genera of, 274 genome organization and transcription, 279–281 medical aspects canine distemper virus, 295 Hendra virus, 294 HMPV (human metapneumovirus), 292–294 measles, 282–290 Menangle virus, 294 mumps, 290 Nipah virus, 294–295 parainfluenza virus, 290–291 respiratory syncytial virus, 291–292 orthomyxoviruses compared, 274 overview, 273–274 replication, 281–282 structure, 274–275 syncytium formation, 279 Parotitis, mumps viral infection and, 290 PARP (poly (ADP-ribose) polymerase), 401 Parvoviridae, 362 Parvovirinae, 363 Parvoviruses, 362–377 autonomous, 48, 363, 365–367, 373–374, 376 B19, 63, 362, 363, 376 binding, 364 classification, 362 dependovirus life cycle, 362–363, 374–376 encapsidation, 371–374 entry, 364–365 genome organization and expression, 374 genomes, 365–367 medical aspects, 376–377 overview, 362–363 receptors, 364 replication, 367–371 rolling-hairpin model, 368–371 size of, 362 structure, 363 Passage, 375 Pasteur, Louis rabies virus vaccine, 5, 6, 261, 271 Patterns of virus infection, 64 PBS1 bacteriophage, 30 PCR See Polymerase chain reaction (PCR) PDZ domain, 435, 439 Peloponnesian War, 547 Penciclovir, 517, 518 Penile cancer, human papillomavirus (HPV)-associated, 433, 440 PEPFAR (President’s Emergency Plan for AIDS Relief), 607, 663–664 PEP (postexposure prophylaxis) for HIV exposure, 651 Pepsin, 82 Perforin, 92, 349 Peripheral tolerance, 124 Permissive cells, 42, 401–402 Persistent infections adenovirus, 445 characteristics of, 63, 66 chronic infections, 68–74 hepatitis B virus (HBV), 687 hepatitis D virus, 691 HIV, 651 in macrophages, 622–623 human T-cell leukemia virus (HTLV-1), 668 latent infections, 74–76 prion diseases, 76–79 715 slow infections, 66–68 Pestivirus, 208 Peyer’s patches, 52, 608 P1 generalized transducing phage, 38 Phage group, 10–15, 21, 34 Phages See Bacteriophages Phagocytes See Macrophages; Neutrophils Pharyngitis adenovirus, 444, 445, 465 herpes simplex virus (HSV), 508 Pharyngoconjunctival fever, 444, 466 Phenotype analysis for personalized therapeutic regimens, 651 Phenotypic mixing, 27, 28 Phi6 (ϕ6) bacteriophage, 47, 150, 158, 167, 325 Phi29 (ϕ29) bacteriophage, 23, 30 Phipps, James, 4, Phlebovirus gene, 350, 352 Phosphatidylinositol 3-kinase (PI3K) signaling pathway, 320, 406, 409 Phospholipase A2 (PLA2), 363, 364–365 Phospholipase C-γ (gamma) (PLC-γ1), 408 Physical barriers against infection, 82 Phytoreoviruses, 149 Picobirnaviruses, 150 Picornaviridae, 171–172 Picornaviruses, 171–206 See also specific viruses assembly and maturation, 198–200 classification, 171 entry, 181–184 poliovirus, 181–183, 184 rhinovirus, 181, 183–184 flaviviruses compared to, 208 genome replication, 194–198 medical aspects coxsackievirus, 205 echovirus, 205 hepatitis A virus, 205–206 poliovirus, 200–203 rhinovirus, 203–205 overview of, 171–172 receptors for coxsackieviruses, 179–180 FMDVs, 180 poliovirus, 177–179 rhinovirus, 173–177 schematic of proteins functioning as, 178 structure, 172–173, 174 transcription, 194–198 translation, 184–187, 192–194 translation initiation sites, 241–242 Pili, RNA phage binding to, 187–188 Pink eye, adenovirus, 444, 445 Pirie, Norman, PKA (protein kinase A), HIV activation of, 634 PKR See Protein kinase (PKR) Placenta, virus dissemination and, 60–63 Placental trophoblasts, HIV entry into, 614–615 PLA2 (phospholipase A2), 363, 364–365 716 IND E X Plaque assay, 11, 17–18 Plaque-forming unit (PFU), 11 Plasma B cells, 109, 137 Plasma membrane, lipid rafts in, 323–324 Plasmids, 15 papillomavirus genomes as, 430 Plasmodium falciparum, 510 Platelet-activating factor, 89 PLC-γ1 (phospholipase C-γ (gamma) 1), 408 Pleurodynea, 205 Plus-sense RNA viruses astroviruses, 356–357 caliciviruses, 355–356 coronaviruses, 235–260 flaviviruses, 207–223 gene expression patterns, 241–242 hepatitis E-like viruses, 357–358 minus-strand viruses compared, 184 picornaviruses, 171–206 retroviruses, 553–596 togaviruses, 224–234 PML (progressive multifocal leukoen­ cephalopathy), 72, 286, 378, 410, 414–417, 647 Pneumocystis carinii, 597, 643, 644 Pneumonia adenovirus, 465 influenza virus, 326, 327 measles virus, 284 parainfluenza virus, 290 Pneumonitis human cytomegalovirus (HCMV) and, 513 MMPV and, 293 Pneumovirus, 274, 275 Pocket factor, 182–183 Poisson distribution function, 244–245 Polar effect, 189 pol gene, retrovirus, 554, 555, 563–564, 568–569, 571–572 Poliomyelitis, paralytic, 172, 178, 200 Poliovirus See also Picornaviruses A particles, 181–182 assembly and maturation, 198–200 entry of, 181–183, 184, 423 genome organization, 186 genome replication, 194–198 medical aspects, 200–203 infection, features of, 200–201 paralytic, 172, 178, 200 postpolio syndrome, 201 vaccination, 171, 172, 201–203 neural invasion, 55 overview of, 172 postpolio syndrome, 68 public knowledge of disease, 658 receptor, 177–179 structure, 172–173, 174, 176 transcription, 194–198 translation, 184–187, 192–194 vaccine, 653 SV40 contamination of, 379, 410, 411 Poliovirus receptor (PVR), 177–179 Pol protein See also Polymerase Gag-Pol polypeptide HIV, 621–622 HIV, 601 retrovirus, 560, 563 Poly(A)-binding protein (PABP), 193, 196, 198 Polyadenylation addition by reiterative transcription in rhabdoviruses, 267 adenovirus transcripts, 454 hepatitis D virus, 691 herpesvirus transcripts, 484 orthomyxovirus, 315 papillomavirus transcripts, 426–429 retroviral transcripts, 569 Poly(ADP-ribose) polymerase (PARP), 401 Poly(A) tail See Polyadenylation Polycistronic mRNAs, 192 Polymerase DNA polymerase adenovirus, 460 DNA-dependent DNA polymerase activity of the reverse transcriptase, 564, 565–566 hepadnavirus, 677, 685 herpesvirus, 488 parvovirus, 367–368 poxvirus, 529, 533 proofreading function in, 462, 488 reverse transcriptase discovery of, 556, 558, 602 DNA-dependent DNA polymerase activity of, 564, 565–566 hepadnavirus, 673 hepatitis B virus (HBV), 674 HIV, low fidelity of, 626, 637 inhibitors, 626, 648, 649, 690 retrovirus, 49, 560, 564–565, 567–568 use in polymerase chain reaction (PCR), 353, 623, 661 use in recombinant DNA technology, 556 RNA phage, 188–191 RNA polymerase arenaviruses, 350 astrovirus, 357 bornavirus, 354 bunyavirus, 351 calicivirus, 356 coronavirus, 243 David Baltimore and, 171, 275 error frequency of, 171, 247 error rate, 329 filovirus, 358 hepatitis E virus, 357–358 influenza virus, 299, 311–315, 317–318, 322, 329, 335–336 lack of proofreading function, 329 paramyxoviruses, 274, 275, 279, 281 picornavirus, 194, 195 poxvirus, 529–533 reovirus, 46, 156–157 rhabdovirus, 262, 264–267 sigma (σ) factors, 32 vaccinia virus, 523 RNA polymerase II (Pol II) adenovirus transcription and, 453 hepadnavirus transcription, 672, 678, 680–683, 685 hepatitis D virus replication, 691, 693 influenza virus requirement for, 314 retrovirus use of, 562–563 SV40 transcription by, 388, 390–394 RNA polymerase III (Pol III), adenovirus transcription and, 456 Polymerase chain reaction (PCR) identification of “tentative” species, 213 reverse transcriptase (RT-PCR), 353, 623, 661 Polymorphism, 113, 114, 117 Polyomaviridae, 378, 379, 407, 419 Polyomaviruses, 378–418 assembly, 399–401 BK virus, 378, 385, 413, 414, 415 DNA replication, 395–399 entry and uncoating, 382–385, 413 gene expression, 386–395 genome organization, 385–390 early region, 385–386 late region, 386 minichromosome, 380, 384–386 origin of replication, 388–390, 395 regulatory region, 386–390 JC virus, 378, 385, 413, 414–415, 416 KI virus, 379, 415, 417 latent infections, 414 LT (large T) antigen DnaJ domain of, 399, 404, 406 DNA replication, participation in, 395–399 neoplasia and, 401–406 regulatory activity of, 391–394 regulatory region recognition by, 386, 388, 392 splicing of mRNA, 394–395 structure, 386, 388, 399 TEF-1, interaction with, 392–393 Merkel cell virus, 379, 417–418 neoplastic transformation, 378, 401–410 overview of, 378–380 persistent infections, 112 progressive multifocal leukoencephal­o­ pathy (PML), 378, 410, 414–417 splicing of viral mRNA, 394–395 structure, 380–382 SV40 in Asian rhesus macaque, 410–411 gene delivery vectors, 418 in humans, 411–414 T antigens gene delivery vectors and, 418 LT (large T), 386–406, 412, 413, 417, 418 MT (middle T), 404, 407–410 neoplasia, 401–410 ST (small T), 386–387, 394–395, 399, 401, 404–407 temporal regulation of transcription, role in, 390–394 INDE X transcription bidirectional, 386 temporal regulation of, 390–394 WU virus, 379, 415, 417 Polyomavirus nephropathy (PVN), 415 Polyomavirus of mice, 378, 379, 390, 402, 404, 407–410 Polyproteins, picornavirus, 172, 185–187, 198–199 Pontiac’s Rebellion, 545 Porcine herpesvirus, 480 Portal, capsid, 372 Portal, herpesvirus, 474, 491 Portal complex, 30 Portals of entry, 50–54 alimentary tract, 52–54 eye, 54 respiratory tract, 51 skin, 51–52 urogenital tract, 54 Portner, Allen, 275 Postexposure prophylaxis (PEP) for HIV exposure, 651 Postherpetic neuralgia, 513 Postpolio syndrome, 68, 201 Posttranscriptional regulatory element (PRE) of hepadnaviruses, 678, 680 Posttransplant lymphoproliferative disease (PTLD), 473, 511–512 Potato spindle tuber viroid, 693 Powell, Colin, 657 Poxviridae, 521 Poxviruses, 521–549 antiviral drugs, 546 assembly, maturation, and release, 534–538 bioterrorism and smallpox, 547–549 clinical syndromes, 543–546 molluscum contagiosum, 544–546 smallpox, 543–544, 545 vaccines, 546–547 DNA replication, 533–534, 535 entry and uncoating, 525–528, 525–529 of EVs (extracellular virions), 528–529 of IMVs (intracellular mature virions), 526–528 evasion of cytokines, 100–101 evasion of host immunity, 101 evasion of interferons, 98 genome organization and expression, 529–533 immune evasion, 538–543 adaptive defenses, 541–543 innate defenses, 538–541 RAP94 (viral transcription specificity factor), 530–532 replication of, 523 size of, 521 structural forms cell-associated enveloped virion (CEV), 525, 536–537 extracellular enveloped virion (EEV), 525, 536–537 extracellular virion (EV), 524–529, 536–537 intracellular enveloped virion (IEV), 524–526, 536–537 intracellular mature virion (IMV), 524–529, 536–537 structure, 523–525, 526 vaccinations, 521, 522, 546–547 VETF (viral early transcription factor), 530–531 VTLF (viral late-gene transcription factor), 533 Yaba virus, 523, 546 pp2A (protein phosphatase 2A), 405, 407, 408 pRb as tumor suppressor protein, 576 inactivation by adenovirus E1A protein, 457 inactivation by Cdk4/cyclin D, 457 inactivation by papillomaviruses, 434–435, 437–438 regulation of cell proliferation by, 403 SV40 LT antigen interaction with, 402–404 SV40 LT protein effect on, 379 PRE (posttranscriptional regulatory element) of hepadnaviruses, 678, 680 President’s Emergency Plan for AIDS Relief (PEPFAR), 607, 663–664 Preston, Richard, 360 Primary gene product, 185 Primary infection, herpesvirus, 472 Primary response genes, 383 Primary transcripts, reovirus, 167 Primer of hepadnaviral reverse transcription, 683 Primer-binding site, retrovirus, 565 Prions, 76–79 Procapsids, herpesvirus, 488–490 Processed pseudogenes, 594–595 Prodrome rabies virus, 270 smallpox, 522, 544 Productive phase of papillomavirus replication, 430 Programmed cell death (apoptosis) See also Apoptosis CTL induction of, 130–131 interferon induction of, 87 Programmed ribosomal frameshift in coronavirus translation process, 242, 243 Progressive multifocal leukoencephalo­ pathy (PML), 72, 286, 378, 410, 414–417, 647 Proheads, phage, 28–29 Promoters adenovirus, 454, 455 hepadnavirus, 676, 678, 679 herpesvirus, 484, 485, 487, 495 HIV, 618, 619 papillomavirus, 425–429 poxvirus, 530, 531 retrovirus, 563, 569 SV40, 391–394 717 Proofreading function in DNA polymerase, 462, 488 lack of, in RNA polymerase, 329 Prophage λ, 35 Prospective studies, 233 Protease astrovirus, 357 flavivirus, 209, 211 herpesvirus, 474 poliovirus, 186–187 retrovirus, 560, 563, 574 ubiquitin-specific, 474 Protease inhibitors for HIV, 648, 653 Proteasome, 119, 120, 121 Protein kinase A (PKA), HIV activation of, 634 Protein kinase (PKR), 86–87, 98–100 activation/induction of, 497 by double-stranded RNA, 86, 167, 641 by interferons, 86–87, 538, 641 inhibition by adenovirus, 464 influenza virus, 319 vaccinia virus, 538 interferon response, role in, 319 Protein phosphatase 2A (pp2A), 405, 407, 408 Protein-tyrosine kinase, 580, 588 Proteoglycans, as AAV receptor, 364 Protomers, picornavirus, 172–173, 198–199 Proto-oncogene, 68, 579–580, 582, 588–591 Protovirus theory, 559 Provirus, 67 avian leukosis virus (ALV), 555 HIV, 618 transcription of retrovirus, 562–563, 564 Provirus hypothesis, 557–559 Prusiner, Stanley, 77 Pseudoknot picornavirus RNA, 195, 196 Rous sarcoma virus, 572 Pseudomonas, phage ϕ6 (phi 6), 150, 158, 167 Pseudomonas phaseolicola, 47 Pseudorabies virus, 480 Pseudorevertants, 400 Pseudotype viruses, 240 Ptashne, Mark, 37 PTLD (posttransplant lymphoproliferative disease), 473, 511–512 Pulse-chase experiment, 26 PVN (polyomavirus nephropathy), 415 PVR (poliovirus receptor), 177–179 Pyrogens endogenous, 89 exogenous, 89 Q Qβ bacteriophage, 187, 190–191 Quantitative reverse transcription polymerase chain reaction (RT-PCR) to quantify plasma HIV RNA levels, 623 Quasiequivalent bonding, 41, 381, 420 718 R IND E X Rabies virus encephalitis, 55 lethality of, 57 neural spread, 55 pathogenicity, 270–272 chronic or latent infections, possibility of, 271–272 dissemination in host, 270–271 incubation period, 270 prodromal phase, 270 vaccine, 5, 6, 261, 271 raf oncogene, 585 Raft culture, 424 Raltegravir, 652–653 Ran-GTP, 321 Ran proteins, 452 RANTES, 611, 616 Raoult, Didier, 524 Ras oncogene, 579, 580, 584 Ras protein, 579, 580, 584 Rat sarcoma virus, 579 Reactivation Epstein-Barr virus (EBV), 502–503 herpes simplex virus (HSV), 496, 498, 507 human cytomegalovirus (HCMV), 504 human herpesvirus (HHV-6), 515 polyomavirus, 414 varicella-zoster virus (VZV), 513–514 Receptor interference, 636 Receptor internalization and degradation (RID) protein, 464 Receptor-mediated endocytosis of adenovirus, 449–450 of flaviviruses, 209 of hepadnavirus, 675–676 of orthomyxovirus, 299 overview, 43 of parvoviruses, 364 of reoviruses, 152, 153 of rhabdoviruses, 263 of rhinoviruses, 183 of togaviruses, 226–227 Receptors activation, 92 coreceptors, 364 CCR5, 604, 610, 611–616 antiviral drugs targeting, 616, 652 CCR5-∆32 allele, 613–614, 615 CD4, 118–119 CD8, 118–119 CXCR4, 604, 610, 611–614, 631 for coxsackievirus, 179 for HIV, 604, 610, 611–616 for parvovirus, 364 for reovirus, 151–152 cytokines, 100–101 dissemination of virus, role in, 57 for adenovirus, 448–449, 450 for coronavirus entry, 237, 238 for parvoviruses, 364 for picornaviruses coxsackieviruses, 179–180 FMDVs, 180 poliovirus, 177–179 rhinovirus, 173–177 for reovirus, 150–153 for retrovirus, 561–562 host range and, 179 identification methods, 151 inhibitory, 92 primary, 364 secondary, 364 Toll-like receptors (TLRs), 83–84, 85 Recoating genetics, 154 Recombination coronavirus, 247–248 somatic, 109 targeted RNA, 249 Reed, Walter, 7, 219 Regulatory region of polyomavirus genome, 386–390 Regulatory T cells (Treg cells), 125 Reid, Ann Reiterative transcription, 267, 279 Release, viral coronaviruses, 251 herpesvirus, 491–493 influenza virus, 325 papillomavirus, 432–433 paramyxovirus, 282 poxviruses, 536, 537 rhabdoviruses, 268–269 Remlinger, Paul, Reoviridae, 149–150 Reovirus, 149–170 See also Orthoreoviruses assembly of particles, 166, 167, 168 bicistronic mRNA, 160 binding and entry into cells, 150–154 capping by, 164–165, 167–168 classification, 47 cores, conversion of ISVPs to, 161–165 evasion of interferons, 98 genome segments, 149–150, 158–161 synthesis of double-stranded RNA, 165–166 transcription, 156–158, 160–161, 164–165, 167–168 translation, 159–160 hosts for, 149–150 interferon and, 167 ISVP (intermediate/infectious subviral particles) conversion of particles to, 155–156 conversion to cores, 161–165 structure, 152 misclassification as echoviruses, 150 neurotropism, 153 overview, 149–150 pathogenesis coltiviruses, 169–170 orthoreoviruses, 168 rotaviruses, 168–169 proteins, table of, 155 recoating genetics, 154 RNA polymerase, particle-associated, 156–157 structure, 151, 152, 154–156, 162–163 uncoating/capsid disassembly, 154–155, 161–162 Replica plating, 35 Replicase calicivirus, 356 circoviruses, 363 coronavirus, 242–243, 250 Replication adenovirus, 460–462 arenavirus, 350 bornavirus, 354–355 bornaviruses, 317 bunyavirus, 351 calicivirus, 356 double-stranded RNA genome, 165–166 end replication problem, 460, 462 filovirus, 358 flavivirus, 209 hepatitis delta virus (HDV), 690–693 influenza virus, 317–318 papillomavirus, 429–432 paramyxovirus, 281–282 parvovirus, 367–371 picornavirus genome, 194–198 poxviruses, 523 reovirus genome, 165–166 retrovirus, 554–555, 562–563, 569–572 rhabdoviruses, 267–268 rolling-circle mode, 370, 431 adenovirus, 460 description of, 370 Escherichia coli phage φX174, 362, 370 hepatitis D virus, 691 herpesvirus, 482, 488, 490 papillomavirus, 431 rolling-hairpin mode, 460 theta structures, 431 togavirus, 228–230 Replication protein A, 396 Replicative intermediate, parvoviruses and, 367–370 Reporter genes, use in pseudotype virus experiments, 240 Rep proteins, parvovirus, 367, 371–376 Reproduction number, 259 Respiratory route of infection, 203 Respiratory syncytial virus, 291–292, 293 Respiratory tract as portal of viral entry, 51 barriers to infection, 82 Respiratory tract infections Hendra virus, 294 human metapneumovirus (HMPV), 284 measles pneumonia, 284 parainfluenza viruses, 290–291 respiratory syncytial virus, 291–292 Reticuloendothelial system, 58 Retinitis, human cytomegalovirus (HCMV) and, 513 Retinoblastoma tumor suppressor protein See pRb Retinoic acid, 591 Retinoic acid-induced gene I product (RIG-I) INDE X as sensor of double-stranded RNA, 85 influenza virus interaction with, 319 Retroelements description of, 593–596 origin of, 559 Retroplasmids, 595–596 Retrospective studies, 233, 292 Retrotransposons, 593 Retroviridae, 553, 600, 602, 667, 669 Retroviruses, 553–596 Abelson murine leukemia virus, 577–578 assembly, maturation, and release, 572–576 Env and budding, 575–576 Gag and Gag-Pol, 572–575 avian erythroblastosis virus (AEV), 582, 585–586 avian hemangioma virus, 579 avian leukosis virus (ALV), 554, 555, 570, 571, 577 Baltimore scheme class IV viruses compared to, 554 classification of, 49, 553, 554 complex, 600–601, 616–618 constitutive transport elements (CTEs), 571, 572 diploid genome, 560 discovery of, 7, 553 DNA retroviruses (See Hepadnaviruses) endogenous, 575, 593 entry, 561–562 env gene, 554, 555, 559, 563–564, 569–571, 576 Env proteins, 561, 563, 575–576, 579 feline leukemia virus, 561, 577 gag gene, 554, 555, 559–560, 563–564, 571 Gag-Pol polypeptide, 563, 568, 569, 571–576 Gag protein, 561, 563, 575–576, 579 gene expression and replication, 569–572 gene therapy vectors, 591–592 genome degradation during reverse transcription, 562, 563 genome organization, 555, 563–564 Gross murine leukemia virus, 553 history of, 553–554, 556–559 HIV, 597–666 human T-cell leukemia viruses, 666–671 integration, 562, 568–569, 570 Jaagsiekte sheep retrovirus (JSRV), 579, 586 Mason-Pfizer monkey virus (M-PMV), 575 Moloney murine leukemia virus, 592 mouse mammary tumor virus, 553, 554, 579 murine leukemia virus (MLV), 554, 567, 572, 575, 577 oncogenesis, 576–591 oncogene-deficient oncogenic retroviruses, 588–591 oncogene-transducing oncogenic retroviruses, 577–588 overview, 553–556 pol gene, 554, 555, 563–564, 568–569, 571–572 Pol polypeptide, 560, 563 replication cycle overview, 562–563 replication strategy, features of, 554–555 reverse transcription, 564–568 simian sarcoma virus (SSV), 582 simple, 616–618 simple versus complex, 554, 555, 600 spumaviruses, 554, 592–593 structure, 559–561 cellular RNA incorporation, 560–561 diploid genome, 560 electromicrograph of, 560 tRNA incorporation, 560, 574 Reverse genetics, 293–294 coronavirus, 248–250 influenza virus, 343 plasmid-based, 343 Reverse transcriptase discovery of, 556, 558, 602 DNA-dependent DNA polymerase activity of, 564, 565–566 hepadnavirus, 673 hepatitis B virus (HBV), 674 HIV, low fidelity of, 626, 637 inhibitors, 626, 648, 649, 690 retrovirus, 49, 560, 564–565, 567–568 use in polymerase chain reaction (PCR), 353, 623, 661 use in recombinant DNA technology, 556 Reverse transcriptase PCR (RT-PCR), 353, 623, 661 Reverse transcription by retroelements, 559, 593 by telomerase, 559 fidelity of, 568 hepadnaviruses, 679–684 inhibitors of, 647–649 priming of, 683 retrovirus, 562, 564–568 Rev protein, HIV, 601, 617, 620–621, 622 Rev-responsive element (RRE), 620 Rex protein, human T-cell leukemia virus (HTLV-1), 669 Rex responsive element (RxRE), 669 Reye’s syndrome, 205, 326 RGD motif, 180 Rhabdoviruses, 261–272 assembly and release, 268–269 cytopathic effect, 269 entry, 263–264 genome organization, 264–267 medical aspects, 269–272 replication, 267–268 structure, 262–263 transcription, 264–268 Rhesus macaque (Macaca mulatta), SV40 virus in, 410–411 Rheumatic fever, 142 Rhinoviruses, 174–176 See also Picornaviruses acute infections, 64–65 719 canyon hypothesis, 176–177 common cold, 172, 203–205, 252 entry, 181, 183–184 evasion of antibodies, 111 receptor and binding, 173–177 respiratory tract as entry portal for, 51 uncoating, 183–184 vaccination, 206 Ribavirin for hepatitis C virus (HCV), 222 structure, 518 Ribonuclease H (RNase H) hepadnavirus, 677 retrovirus, 560, 564–566 Ribonuclease L (RNase L), 86, 87, 98–99 action of, 87 activation by 2′-5′-oligoadenylate synthetase, 538–539 herpes simplex virus (HSV-1) impairment of, 497–498 influenza virus blockage of activation, 319 inhibition by vaccinia virus, 99, 539 interferon response, role in, 319 RNA activation of, 86, 87 Ribonucleoprotein complexes of minus-strand RNA viruses, 265 Ribonucleotide reductase of poxviruses, 533 Ribosome frameshifting by Rous sarcoma virus, 571–572 in coronavirus translation process, 242, 243 readthrough of termination codon, 191 scanning hepadnavirus translation and, 679 model for initiation of translation, 281, 425 process, 228 Ribozyme, 691 RID (receptor internalization and degradation) protein, 464 Rift Valley fever virus, 350 rII genes, 33, 34–35 Rimantadine, 308, 325, 344 Rinderpest virus, 288, 289 Ring vaccination strategy, 54 Rise period, 12 Rituximab (Rituxan), 416–417 RNA double-stranded RNA activation of 2′-5′-oligoadenylate synthetase, 319 interferon induction by, 84, 85 protein kinase A activation by, 167, 641 synthesis by reovirus, 165–166 metabolism in infected cells, 25–27 miRNA, SV40 and, 413–414 mRNA (See Messenger RNA (mRNA)) SV40 miRNA, 413–414 tRNA molecules, in retrovirus particles, 560, 574 RNA-dependent RNA polymerase coronavirus, 243 reovirus, 156–157 720 IND E X RNA editing, paramyxoviruses and, 280–281 RNA helicase in coronavirus replicase complex, 243 RNA intermediate of hepadnaviruses, 672, 685 RNA phages, 187–192 RNA polymerase arenaviruses, 350 astrovirus, 357 bornavirus, 354 bunyavirus, 351 calicivirus, 356 coronavirus, 243 David Baltimore and, 171, 275 error frequency of, 171, 247, 329 filovirus, 358 hepatitis E virus, 357–358 influenza virus, 299, 311–315, 317–318, 322, 329, 335–336 lack of proofreading function, 329 paramyxoviruses, 274, 275, 279, 281 picornavirus, 194, 195 poxvirus, 529–533 reovirus, 46, 156–157 rhabdovirus, 262, 264–267 sigma (σ) factors, 32 vaccinia virus, 523 RNA polymerase II (Pol II) adenovirus transcription and, 453 hepadnavirus transcription, 672, 678, 680–683, 685 hepatitis D virus replication, 691, 693 influenza virus requirement for, 314 retrovirus use of, 562–563 SV40 transcription by, 388, 390–394 RNA polymerase III (Pol III), adenovirus transcription and, 456 RNA priming, 488 RNase H See Ribonuclease H (RNase H) RNase L See Ribonuclease L (RNase L) RNA synthesis, picornavirus, 194–198 RNA tumor viruses, 553, 554 See also Retroviruses RNA viruses, 346–361 arenaviruses, 347–350 astroviruses, 356–357 Baltimore classification system, 46–49 bornaviruses, 352–355 bunyaviruses, 250–253 caliciviruses, 355–356 coronaviruses, 235–260 emerging pathogens, 252 filoviruses, 358–361 flaviviruses, 207–223 genome size, theoretical upper limit of, 171 hepatitis E-like viruses, 357–358 host range, 179 orthomyxoviruses, 296–345 paramyxoviruses, 273–295 picornaviruses, 171–206 reovirus, 149–170 retroviruses, 553–596 rhabdoviruses, 261–272 togaviruses, 224–234 Roberts, Richard, 394, 455 Robinson, William, 275 Rocket motility, 538 Rocky Mountain spotted fever, 169 Rolling-circle replication adenovirus, 460 description of, 370 Escherichia coli phage φX174, 362, 370 hepatitis D virus, 691 herpesvirus, 482, 488, 490 papillomavirus, 431 Rolling-hairpin model, 368–371, 460 Roseola, 514 Ross River virus, 232 RotaShield, 169 Rotaviruses, 149–150, 153, 156, 168–169 as emerging disease, 599 entry, 307 Rous, Peyton, 7, 8, 421, 434, 553, 556, 588 Rous sarcoma virus (RSV) See also Retroviruses as oncornavirus, 434, 554 diploid genome, 560 discovery of, 7, 8, 553, 556 entry, 561–562 integration of, 557 in vitro focus-forming assay, 556–557 oncogene, 569 ribosomal frameshifting, 571–572 src gene, 577–578 structure, 559–561 Temin’s work with, 556–558, 559 translation, 571–572 tryptophan tRNA as primer for reverse transcription, 560, 565 Rowe, Wallace P., 445–446 Rozenbaum, Willy, 604 RRE (Rev-responsive element), 601 RSV See Rous sarcoma virus (RSV) Rta protein, Epstein-Barr virus (EBV), 502–503 RT-PCR (reverse transcriptase PCR), 353, 623, 661 Rubella virus, 224, 232–234 fetal infection, 62–63 Rubin, Harry, 556 Rubulavirus, 274, 275, 294 Rwanda, AIDS in, 664 RXRE (Rex responsive element), 669 S Sabin, Albert polio vaccine, 171, 201–203, 653, 658 reovirus classification and naming, 150 Salk, Jonas, 171, 201–203, 245, 653, 658 Salvage therapy, 651 Samson, Michael, 613 Sarcomas, 646 SARS-CoV See Severe acute respiratory syndrome (SARS) Satellite virus hepatitis delta virus, 690–694 Sputnik, 524 Scaffolding proteins adenovirus and, 463 herpesvirus assembly, 489 Schistosoma mansoni, 216 Schlesinger, Max, Schramm, Gerhard, 15 SCID (severe combined immunodeficiency disease), 94 Sclera, 54 Scrapie, 76, 77, 78 Scribble protein, 439 SDF-1, 611 Secondary transcripts, reovirus, 167 Secretory IgA, 294 Sedornaviruses, 149 Sefton, Bart, 588 Selection negative, 139 positive, 139 Self tolerance, 137–139 Selzentry, 652 Semiconservative DNA synthesis, 685 Semliki Forest virus, 227, 228 Sendai virus capsid structure, 40 genome organization, 279, 280 RNA editing, 281 Senescence p53 protein and, 438 telomere length in cells, 437 Septic shock, 348 Sequelae, 68, 285, 508 Sequestered host antigens, 143 Serine/threonine kinase, 580, 581 Serotypes, 65, 419 Severe acute respiratory syndrome (SARS), 252–260, 599 ACE2 receptor for, 253, 257–258 ADE (antibody-dependent enhancement), 217 cross-species transmission of, 252 entry into cells, 238, 240 future outbreaks, 258–259 immunopathology of, 253 outbreak (2003), 254–256 outbreak (2004), 254, 256 pathogenesis, 252–253 transmission, 252–253 zoonotic, 256–258 Severe combined immunodeficiency disease (SCID), 94 Sexual intercourse, HIV transmission by, 54 Sexually transmitted diseases See also specific diseases human papillomavirus (HPV), 421, 433, 441–442 transmission of HIV, 606–607, 655–656 Shakespeare, William, 472 Shalala, Donna, 659 Sharp, Philip, 394, 455 Shc protein, 408–409 SH2 domains, 580, 582, 589, 590 SH3 domains, 582, 583, 590 Shine-Dalgarno sequences, 192 Shingles (herpes zoster), 472, 513–514, 519 INDE X Shinrikyo, Aum (terrorist group), 548 Shipyard eye, 466 Shope, Richard E., 328, 421, 434, 546 Shope fibroma virus, 546 Short interspersed repeat elements (SINEs), 593–594 Sialic acid, reovirus binding, 152, 153 Sigma (σ) factors, 32 Sigma (σ1) protein, reovirus, 151 Signalase, 211 Signaling pathways apoptosis prevention and, 320 growth-stimulatory signals, response to, 579–582 JAK/STAT signaling pathway, 85–86, 98, 101, 134, 687 phosphatidylinositol 3-kinase (PI3K) signaling pathway, 320, 406, 409 Signal peptidase, cellular, 230–231 Signal recognition particle (SRP), 230 Signal sequences of flavivirus proteins, 210–211, 212 of integral membrane proteins, 44 signalase-mediated cleavage, 211 togavirus and, 230–231 Simian immunodeficiency virus (SIV), 600 nef mutants, 636 simian AIDS, 410 SIV/macaque model, 630, 654 sooty mangabey immune response to, 642–643 Vpr-deficient mutants, 639 Vpx protein, 639 Simian sarcoma virus (SSV), 581 Simian virus 40 See SV40 Sindbis virus, 232 antibody response to, 105 assembly, 232 gene expression, 229 structure, 225, 226, 227 SINEs (short interspersed repeat elements), 593–594 Single-stranded RNA viruses, 346–361 arenaviruses, 347–350 astroviruses, 356–357 bornaviruses, 352–355 bunyaviruses, 250–253 caliciviruses, 355–356 filoviruses, 358–361 hepatitis E-like viruses, 357–358 Sin Nombre virus, 350, 351 Sinusoids, 58 sis oncogene, 582 SIV See Simian immunodeficiency virus (SIV) Sixth disease, 514 Skin as portal of viral entry, 51–52 barriers to infection, 82 structure of, 51 Slow infections, 66–68 SMAD3, 495 Small DNA tumor viruses, 378 Smallpox bioterrorism and, 548–549 clinical presentation, 543–544, 546 eradication program, 522, 546 genetic resistance to, 544, 545 history, 4, 521–522, 545 surveillance and containment strategy, 522 transmission, 544 vaccination, 4–5, 521, 522, 546, 547, 548, 549 variolation, Smith, Kendall, 602 SNARE proteins, 303–304, 306, 307 Somatic hypermutation, 103, 109, 595 Somatic recombination, 109 Sooty mangabey, lentiviruses by, 642 SOS repair system, 38, 580 South Africa, AIDS in, 665–666, 667 Spanish flu, 200, 326, 332 See also Influenza, pandemic (1918) Specialized transduction phage, 38 Spike protein, 44 of coronaviruses, 236–240, 251 Spliceosome, impairment by HIV-1 mRNA, 484, 485 Splice sites, of papillomavirus transcripts, 425–429 Splicing adenovirus, 454, 455, 457 alternative, 243, 244 adenovirus transcripts, 454, 457 bornavirus mRNAs, 354 discovery of, 455 herpesvirus transcripts, 484 HIV mRNAs, 601–602, 617, 620–621 papillomavirus transcripts, 428 SV40 transcripts, 394–395 SPO1 bacteriophage, 30 Spumaviruses, 554, 592–593 Sputnik, 524 Squamous intraepithelial lesions, 433, 436, 439, 440 src gene, 577–578, 580 Src kinases activation by SV40 MT antigen, 407–410 inactivation by Epstein-Barr virus (EBV), 501 poxvirus release and, 537 Src protein, 580, 581, 582, 584, 587–588, 589 SRP (signal recognition particle), 230 SSPE (subacute sclerosing panencephalitis), 66–67 SSV (simian sarcoma virus), 581 St Louis encephalitis virus, 220 Stahl, Franklin, 25, 27 Stalin, Joseph, 521 Stampfer, Martha, 264, 275 Stanley, Wendell, 9–10 STAT proteins, 86 inhibition by hepadnaviruses, 687 Stavudine (d4T), 518 Stem-loop, picornavirus RNA, 195, 196 STEP trial of Merck HIV vaccine, 654–655 Stone, Henry, 275 Stop-transfer sequence, 230–231 Strain, 248 721 Strand displacement in poxvirus DNA replication, 534 Streptococcus pyogenes, 142 Strong stop DNA, 565 Structural plasticity of HIV, 640 Structure, viral adeno-associated viruses (AAVs), 363, 364 adenoviruses, 446–448 animal virus, 39–42 coronaviruses, 236–237 dengue virus, 208 filoviruses, 358 flaviviruses, 208–209 hepadnaviruses, 673, 674–675 hepatitis B virus (HBV), 673, 674–675 herpes simplex virus (HSV), 473–474 herpesviruses, 473–474 HIV, 605–606 influenza virus, 298–299 orthomyxoviruses, 298–299 papillomaviruses, 420–421 paramyxoviruses, 274–275 parvoviruses, 363 picornaviruses, 172–173, 174 poliovirus, 172–173, 174, 176 polyomaviruses, 380–382 poxviruses, 523–525, 526 reovirus, 151, 152, 154–156, 162–163 retroviruses, 559–561 rhabdoviruses, 262–263 Rous sarcoma virus (RSV), 559–561 Sendai virus, 40 Sindbis virus, 225, 226, 227 SV40, 380–382 T-even phages, 22–24 tobacco mosaic virus (TMV), 40 togaviruses, 225, 226 vaccinia virus, 523–525 vesicular stomatitis virus, 40 Subacute sclerosing panencephalitis (SSPE), 66–67, 285–288 Subgenomic mRNA, togavirus, 229, 231 Sub-Saharan Africa, HIV/AIDS in, 662–666 Subunit vaccine hepatitis B virus (HBV), 689 respiratory syncytial virus, 292 Subviral pathogen, 690–691, 693 Summers, Jesse, 685 Superantigen, 293 Superinfection, 32 Superspreaders, SARS, 253 SV40 See also Polyomaviruses as contaminant in vaccines, 379, 410, 411 entry, 382–385, 413 gene delivery vectors, 418 genome organization, 385–390 early region, 385–386 late region, 386 minichromosome, 380, 384–386 origin of replication, 388–390, 395 regulatory region, 386–390 genome sequencing, 379–380 in Asian rhesus macaque, 410–411 722 IND E X SV40 (continued) in humans, 411–414 LT (large T) antigen DnaJ domain of, 399, 404, 406 DNA replication, participation in, 395–399 neoplasia and, 401–406 regulatory activity of, 391–394 regulatory region recognition by, 386, 388, 392 splicing of mRNA, 394–395 structure, 386, 388, 399 TEF-1, interaction with, 392–393 miRNA, 413–414 overview of, 378–380 structure, 380–382 T antigens gene delivery vectors and, 418 LT (large T), 386–406, 412, 413, 417, 418 MT (middle T), 404, 407–410 neoplasia, 401–410 ST (small T), 386–387, 394–395, 399, 401, 404–407 temporal regulation of transcription, role in, 390–394 uncoating, 384–385 Swaziland, AIDS in, 662 Swine influenza, 342 Swinepox virus, Synaptobrevin, 303 Syncytin, 138 Syncytium formation paramyxoviruses and, 279 vaccinia virus and, 527, 537–538 Syntaxin, 303 Syphilis, 659 Systemic illness, definition of, 216 Systemic infection, definition of, 55 T Tak (Tat-associated kinase), 619–620 T antigens, of SV40 gene delivery vectors and, 418 LT (large T), 386–406, 412, 413, 417, 418 MT (middle T), 404, 407–410 neoplasia, 401–410 ST (small T), 386–387, 394–395, 399, 401, 404–407 temporal regulation of transcription, role in, 390–394 TAP/NFX, 321 TAP transporter, 496–497 Targeted RNA recombination, 249 Targeted therapy approach, 468 Target theory, 243, 244–245 TAR (transactivation response) element, 601, 619, 641 TATA-binding protein (TBP), 393 TATA box, 388–390 TATA box-like sequence, 388–390 Tat-associated kinase (Tak), 619–620 Tat protein HIV, 601, 619–620, 621, 622, 632, 639, 641 Taubenberger, Jeffery, 327, 330, 333, 334 Tax protein, human T-cell leukemia virus (HTLV-1), 668–671 T2 bacteriophage in Hershey-Chase experiment, 14 T4 bacteriophage, electron micrograph of, 13 TBP (TATA-binding protein), 393 T-cell-mediated defenses, adenoviruses evasion of, 465 T-cell receptors, 113–115, 117–120, 122–124, 126–127, 129–130 T cells See also Cell-mediated immunity; specific T cell types anergic, 632–634 antiviral cytokines and, 131–132 CD4 T cells, 118 CD4 coreceptor, 118–119 delayed-type hypersensitivity and, 218 HIV infection of, 609, 610–616, 623–636 human T-cell leukemia virus (HTLV-1) targeting of, 603, 667–669 role in adaptive immune response, 629 role in immune defenses against fungi, 645 CD8 T cells blockage of herpes simplex virus (HSV-1) reactivation by, 498–499 CD8 coreceptor, 118–119 delayed-type hypersensitivity and, 218 hepatitis C virus modulation of response, 221–222 clonal selection, 114 cross-reactivity, 115 cytotoxic T lymphocytes (CTLs) activation of, 128–129 control of Epstein-Barr virus (EBV) infection by, 501–502 hepatitis B virus (HBV) and, 686–687 HIV infection and, 623–625, 634–637, 639, 642–643 inhibition of antigen presentation to, 132–134 mechanism of action, 129–131 MHC molecule interaction, 114–115, 118–119, 121–122, 124, 128–130, 132–134 poxvirus countermeasures against, 541–543 helper T cells (Th cells) activation of, 124–126 B cell interaction, 115, 126–128 classes of, 124–126 Epstein-Barr virus (EBV) infections and, 503 inhibition of antigen presentation, 134 superantigen activation of, 293 hepatitis B virus (HBV) and, 69 interferon effect on, 88 memory, 125, 137 HIV infection of, 623 HIV latency in, 635 naïve, 124–125 receptors, 89 regulatory, 125 3TC (lamivudine), 649, 651 TEF-1 (transcription-enhancing factor 1), SV40 LT antigen and, 392–393 Tegument, herpesvirus, 472, 474, 480–481, 491–492 Telbivudine for hepatitis B virus, 690 Telomerase, 368 inactivation by papillomavirus, 437 reverse transcription and, 559 Telomeres, 367, 368 Temin, Howard David Baltimore’s comments on, 558–559 in vitro focus-forming assay, 556–557 reverse transcriptase discovery, 556, 602 Rous sarcoma virus and, 556–558 Temperate phage, 15 Temperature sensitive (ts) mutant, 32 Tenofovir for hepatitis B virus, 690 structure of, 649 “Tentative” species, 213 Teratogenic viruses, 62 Terminal protein, adenoviral genome, 444, 448, 460, 461 Terminal repetition of poxvirus genomes, 529 Terminal resolution, 371, 373 Termination signal, in poxvirus transcription, 531 T-even phages as model system, 20–22 circularly permuted genomes, 484 discovery of, 21 modified bases, 30 one-step growth experiment of T4, 12 one-step multiplication of T2, 13 phage release, 32–33 regulation of gene expression, 30–32 structure and entry, 22–24 unique features of, 30–33 TflIh, 619–620 T gene, 33 TGEV (transmissible gastroenteritis virus), 249 TGF-β (transforming growth factor beta), 125, 495 Th cells activation of, 124–126 B cell interaction, 115, 126–128 classes of, 124–126 Epstein-Barr virus (EBV) infections and, 503 inhibition of antigen presentation, 134 superantigen activation of, 293 Theiler, Max, 219 Theiler’s murine encephalitis virus, 141, 143, 172, 286 Thermolysin, 304 Theta (θ) replication, 488 Theta structures, 431 INDE X Thimerosal, 291 Thogoto virus, 297 Thogovirus (genus), 297 Thompson, Tommy, 654 Thucydides, 547 Thymic selection, 139 Thymidine kinase of poxviruses, 533 Thymidylate kinase of poxviruses, 533 Tight junctions, 57, 60 TIR (Toll/IL-1 receptor) domain, 540 Tissue microenvironment, influence on human papillomavirus (HPV) infection, 439–440 TLM (translocation motif), hepadnavirus, 675–676 TLRs See Toll-like receptors (TLRs) TNF See tumor necrosis factor (TNF) TNF-associated factor (TRAF6), inhibition by vaccinia virus, 540 Tobacco mosaic virus (TMV), 7, 15 assembly of, 251 capsid structure, 40 T-odd phages, 21 Togaviridae, 207–208, 224 Togaviruses, 224–234 assembly and maturation, 231–232 entry, 225–228 epidemiology and pathogenesis Chikungunya virus, 232 eastern equine encephalitis virus, 232 Ross River virus, 232 rubella virus, 232–234 Sindbis virus, 232 Venezuelan equine encephalitis virus, 232 western equine encephalitis virus, 232 flavivirus compared to, 225 gene expression, early and late phases of, 229 genome organization, 228 genome replication, 228–230 genome size, 225 overview of, 224–225 structure, 225, 226 transcription, 228–229 translation, 228–230 translation initiation sites, 241–242 Tolerance neonatal, 141 self, 137–139 Toll/IL-1 receptor (TIR) domain, 540 Toll-like receptors (TLRs), 83–84, 85 inhibition by poxviruses, 541 inhibition by vaccinia virus, 540 Toll protein, 84 Tonsils, isolation of adenovirus from, 445–446 Topoisomerase of poxviruses, 533 topoisomerase I, 396 Torque teno mini virus (TTMV), 674 Torque teno virus, 144, 674 Tospovirus genus, 350, 352 TOUCH Prescribing Program, 417 Toxin, Toxoplasmosis in AIDS patients, 644, 647 TRAF6 (TNF-associated factor 6) inhibition by vaccinia virus, 540 TRAIL receptors, 464 Transactivation response (TAR) element, 601, 619, 641 Transcriptase, 46, 264 Transcription adenovirus, 452–456 arenaviruses, 350 bornavirus, 354–355 bunyavirus, 351, 352 conservative, 157–158 coronavirus, 243, 245–247 hepadnavirus, 672, 678, 680 hepatitis delta virus (HDV), 691 herpesvirus, 483–487 human immunodeficiency virus (HIV), 617–621 influenza virus, 311–317 of retroviral integrated provirus, 562–563, 564 papillomavirus, 425–429 paramyxoviruses, 279–281 picornavirus, 194–198 polyomavirus, 386, 390–394 poxvirus, 530–533 primary versus secondary, in reoviruses, 167–168 reiterative, 267, 279 reovirus, 156–158, 160–161, 164–165, 167–168 rhabdoviruses, 264–268 semiconservative, 157–158 togavirus, 228–229 Transcription-enhancing factor (TEF-1), SV40 LT antigen and, 392–393 Transcription initiation site, togavirus, 229 Transcytosis by adenovirus, 449 by HIV, 614 of IgA molecules, 110 M cells and, 52–53 Transduction bacteriophage λ, 38 generalized, 38 specialized, 38 Transformation, neoplastic by adenoviruses, 456–458, 459 by polyomaviruses, 378, 401–410, 459 by SV40, 401–410 differences between normal and transformed cells, 379 hit-and-run hypothesis/mechanism, 402, 459 permissive cells, 401–402 susceptible cells, 401 Temin’s quantitative assay for, 557 Transformation of bacteria, Transformation zone of cervix, 440–441 Transforming genes, adenovirus, 456–458, 459 Transforming growth factor beta (TGF-β), 125, 495 Transforming units, 557 723 Transgenic mice, 94 Translation arenaviruses, 350 bunyavirus, 351, 352 calicivirus, 356 coronavirus, 238, 240–243 flavivirus, 209, 210, 212 hepadnavirus, 678–679 initiation via ribosome scanning process, 228 leaky scanning recognition of start site, 160 papillomavirus, 425 picornaviruses, 184–187, 192–194 reovirus, 159–160 retrovirus, 571–572 RNA phage, 188–1914 togavirus, 228–230 Translation initiation complex, 191 Translation initiation factors, eukaryotic, 192–194 Translation initiation site coronavirus, 242 flavivirus genome, 210 papillomavirus, 425–429 paramyxoviruses, 281 reovirus mRNA, 160 RNA phages, 188–191 togavirus genomic RNAs, 228–231 Translocation complex, 230–231 Translocation motif (TLM), hepadnavirus, 675–676 Transmissible gastroenteritis virus (TGEV), 249 Transmissible spongiform encephalopathy, 76–79 Transmission, viral acquired immunodeficiency syndrome (AIDS) intravenous drug use, 607, 656–657 mother-to-child, 61, 62, 607, 614–615, 659 public’s beliefs concerning, 608 sexual, 53, 606–607, 655–656 sub-Saharan Africa, 664 adenoviruses, 465 arboviruses, 52, 55 general principles of, 214–215 by arthropod vectors, 214–215 hepadnaviruses, 685–690 hepatitis B virus (HBV), 685–690 hepatitis C virus (HCV), 220–221 hepatitis delta virus (HDV), 693–694 human herpesvirus (HHV-6), 514 human T-cell leukemia viruses (HTLVs), 667 influenza virus, 301 papillomavirus, 432–433 severe acute respiratory syndrome (SARS), 252–253 zoonotic, 256–258 smallpox, 544 transovarial, 215 yellow fever, 219 Transovarial transmission, 215 724 IND E X Transplant arterial disease, human cytomegalovirus (HCMV) and, 513 Transporter associated with antigen processing (TAP), 119, 120, 121, 122 Transposons, 593 Treatment of infections See Antiviral drugs; specific viruses Trentin, J J., 446 Trifluridine, 518 tRNA molecules in retrovirus particles, 560, 574 Trophoblasts, HIV entry into placental, 614–615 Tropical spastic paraparesis (TSP), 667, 670 Tropism hepadnavirus, 673, 685 papillomaviruses, 420 receptor preference as determinant of, 153 receptor role in, 42 reovirus, 153 Tryptase Clara, 302, 309, 334, 335, 340 Tryptic digests of proteins, 185 T-SNARE, 303–304 TSP (tropical spastic paraparesis), 667, 670 Ts (temperature sensitive) mutant, 32 TTMV (torque teno mini virus), 674 TT virus, 674 Tuberculosis AIDS and, 644–645 vaccine, 655 Tumor necrosis factor (TNF), 88–89 adenovirus inhibition of, 464 inhibition by poxviruses, 540, 541 Tumor suppressor proteins, 136, 402, 576 See also p53; pRb Twort, Frederick W., Tysabri (natalizumab), 415, 416–417 U Ubiquitin, 119 Ubiquitin ligases, 543 Ubiquitin-proteasome pathway, 119, 120, 121 Ubiquitin-specific protease, 474 UDPG (uridine diphosphate glucose), 31 Ultraviolet (UV) inactivation studies of rhabdoviruses, 264, 266 Uncoating adenovirus, 450–452 papillomaviruses, 423–424 poxviruses, 527, 532 reovirus, 154 rhinovirus, 183–184 SV40, 384–385 togavirus, 227–228 vaccinia virus, 527 Upstream regulatory region (URR) papillomavirus, 427–428 Uracil dimers, formation by UV irradiation, 266 Uracil-DNA glycosylase, 686 Urbani, Dr Carlo, 255 Urethritis, adenovirus, 466 Uridine diphosphate glucose (UDPG), 31 Urogenital infections, adenovirus, 466 Urogenital tract as portal of viral entry, 54 barriers to infection, 82 URR (upstream regulatory region), papillomavirus, 427–428 UV target size of coronavirus gene, 243, 244–245, 247 UV (ultraviolet) inactivation studies of rhabdoviruses, 264, 266 V Vaccination herd immunity, 522 ring vaccination strategy, 549 Vaccines ADEM (acute disseminated encephalomyelitis) and, 285 adenovirus, 446 adenovirus-based, 469–470 HIV vaccine, 469–470 influenza virus vaccine, 470 antibody-dependent enhancement (ADE) as hindrance to development of, 216–217 attenuated, 5, 201 DNA, 344, 655 Gardasil, 441–442, 443 hepatitis A virus (HAV), 206 hepatitis B virus (HBV), 689 hepatitis C virus (HCV), 223 herpesvirus, 519–520 history of development, 4–6 HIV, 217, 469–470, 622, 653–655 human papillomavirus (HPV), 441–442, 443 inactivated, 201 influenza virus, 298, 337–339, 343–344, 470, 599 mandating use of, 442 measles, 273, 282, 289–290 MMR, 234, 285, 289–291 MMRV, 234 mumps, 290 natural immunity compared, poliovirus, 171, 172, 201–203, 653 rabies, 5, 6, 261, 271 respiratory syncytial virus, 292–293 rotavirus, 169 rubella, 233–234 safety of, 291 smallpox, 4–5, 521, 522, 546, 547–549 subunit, 292, 689 SV40 as contaminant in, 379, 410, 411 for tuberculosis, 655 vaccinia, varicella-zoster virus (VZV), 519 yellow fever, 218, 219, 687 Vaccinia virus, assembly, maturation and release, 534–538 CTL evasion strategies, 542–543 DNA replication, 533–535 entry and uncoating, 302, 525–529 of EVs (extracellular virions), 528–529 of IMVs (intracellular mature virions), 526–528 evasion of complement, 102 evasion of interferons, 98–99 extracellular virion, 302 genome organization and expression, 529–533 immune evasion, 538–543 adaptive defenses, 541–543 innate defenses, 538–541 natural host of, 523 RNA polymerase of, 523 smallpox vaccine, 522, 546 structure, 523–525 syncytium formation, 527, 537–538 viroceptors, 538 Vaccinia virus intermediate transcription factor (Vitf), 532–533 Vaginal epithelium as barrier to infection, 82 HIV transmission across, 608–609 Valacyclovir, 517, 519 Variable (V) domain, antibody, 106, 107 Variant, 248 Varicella See Chicken pox Varicella-zoster virus (VZV) AIDS and, 644 antiviral drugs for, 518 clinical syndromes, 513–514 chicken pox, 472, 513 herpes zoster (shingles), 472, 513–514 postherpetic neuralgia, 513 latent infections, 75 reactivation, 513–514 respiratory tract as entry portal for, 51 vaccine, 519 Variolation, Variola virus, 521 See also Smallpox antiviral drugs, 546 clinical syndromes, 544 eradication of, 522, 546 genetic resistance to, 544, 545 immune evasion strategies of, 538 reference stocks of, 522, 549 terminal repetition sequences in genome, 529 Varmus, Harold, 556, 578, 579, 580, 587 naming of HIV, 603 on support for AIDS research, 601 Vascular endothelial growth factor (VEGF), 468–469 VCAM-1, 416 Venezuelan equine encephalitis virus, 232 Vertical transmission, 70 Vesicular stomatitis virus (VSV), 261–270 capsid structure, 40 cytopathic effect, 269 entry of, 383 G protein of, 475 pathogenicity, 261, 270 Vesiculovirus, 261, 270 VHS (virus-associated host shutoff) protein, 480, 496 INDE X Vif protein, HIV, 103, 601, 617, 637 Viral factories, poxviruses and, 534 Viral ribonucleoprotein segments of influenza virus, 299–300, 308–311, 322–325 Viral set point, HIV, 624, 625, 626, 627–629 Viremia arbovirus, 214 dengue virus, 216 hepatitis B virus (HBV), 685, 687 hepatitis C virus (HCV), 221 measles virus, 283–284 persistent, 58 primary, 55 rotavirus, 168 secondary, 55 West Nile virus, 215 Viroceptors, of poxviruses, 538, 539, 540 Viroids, 690–691, 693 Virophage, 524 Viroplasm, 535 Viroporin, 385, 401 Viroreceptors, 100 Virus as alive, 16–17 definition of, 15–16 origin of, 17 Virus-associated host shutoff (VHS) protein, 480, 496 Virus-like particles (VLPs), 128, 138 coronavirus, 237, 251 papillomavirus, 422–424 SV40-based gene delivery vectors, 418 Visna/maedi virus of sheep, 600 Vitalism, 10 Vitamin A deficiency, 284 Vitf2, role in poxvirus transcription, 532, 533 Vitf (vaccinia virus intermediate transcription factor), 532, 533 Vitronectin, 448 Vogt, Peter, 578 Voltage-clamp procedure, 308 VP16 See Alpha-trans-inducing factor (α-TIF) Vpr protein, HIV, 601, 617, 638–639 Vpu protein, HIV, 601, 617, 636–637 Vpx protein, HIV, 639 V-SNARE, 303 VSV See Vesicular stomatitis virus (VSV) W Wakefield, A J., 291 Warts, 73, 420, 421, 433, 434, 441 Washington, George, 521 Watson, James, 380 Weinberg, Robert, 578 West African mouse (Mastomys natalensis), 348 Western blot test for HIV, 660 Western equine encephalitis virus, 17, 18, 232 West Nile virus, 213–214, 215, 220, 599 White-toothed shrew (Crocidura leucodon) as reservoir for Borna disease virus, 352 Wild-type, 28, 248 Wimmer, Eckard, 185 WIN compounds, 183 Window of infectivity before seroconversion (window period) of HIV, 624 725 Winthrop, Sterling, 183 Wood, W B., 28 Woodchuck hepatitis virus, 672 hepatocellular carcinoma model, 689 Wood tick (Dermacentor andersoni), coltivirus transmission by, 169 WU virus, 379, 415, 417 X X-ray diffraction analysis of nonenveloped viruses, 209 Y Yaba virus, 523, 546 Yellow fever vaccine hepatitis B virus (HBV) contamination of, 687 vaccine-associated neurotropic adverse events, 218 Yellow fever virus, 217–218, 599 Yersinia pestis, 153, 494, 544 YF 17D (yellow fever vaccine), 218 Z Zalcitabine, 649 Zanamivir, 325, 336, 342 Zidovudine (ZDZ), 647–648, 649 Zimbabwe, AIDS in, 662 Zinc-binding cell surface peptidases, 238 Zinkernagel, Rolf, 114 Zoonotic outbreaks of coronaviruses, 248 Zostavax, 519 Zta protein, Epstein-Barr virus (EBV), 502–503 zur Hausen, Harald, 421, 443, 605 Zymogens, 95