HIV AND AIDS – UPDATES ON BIOLOGY, IMMUNOLOGY, EPIDEMIOLOGY AND TREATMENT STRATEGIES Edited by Nancy Dumais HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies Edited by Nancy Dumais Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Used under license from Shutterstock.com First published October, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies, Edited by Nancy Dumais p. cm. 978-953-307- 665 -2 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 From the Laboratory to the Clinic: HIV and Cellular Interactions 1 Chapter 1 Functions of the Lentiviral Accessory Protein Nef During the Distinct Steps of HIV and SIV Replication Cycle 3 Luciana J. Costa, Luiza M. Mendonça and Thatiane L. Sampaio Chapter 2 The Role of Human Immunodeficiency Virus Type 1 (HIV-1) Proteins and Antiretroviral Drug Therapy in HIV-1-Induced Oxidative Stress 41 Edna Maria Vissoci Reiche and Andréa Name Colado Simão Chapter 3 HIV Toxins: Gp120 as an Independent Modulator of Cell Function 69 Leonor Huerta and César N. Cortés Rubio Chapter 4 HIV Recombination and Pathogenesis – Biological and Epidemiological Implications 97 Nitin K. Saksena, Dominic E. Dwyer and Bin Wang Chapter 5 Insulin-Like Growth Factor System in HIV/AIDS: A Structure Based Approach to the Design of New Therapeutics 125 Monalisa Swain, Harsha Balaram and Hanudatta S. Atreya Chapter 6 Cellular Restriction Factors: Exploiting the Body’s Antiviral Proteins to Combat HIV-1/AIDS 143 Jenna N. Kelly, Jessica G.K. Tong, Clayton J. Hattlmann,Matthew W. Woods and Stephen D. Barr Chapter 7 Retroviral Host Cell Factors: TRIM5, APOBEC3G and Cyclophilins 183 Ryuta Sakuma and Hiroaki Takeuchi VI Contents Part 2 From the Laboratory to the Clinic: HIV and the Immune System 197 Chapter 8 HIV Without AIDS: The Immunological Secrets of Natural Hosts 199 Zachary Ende, Michelle Bonkosky and Mirko Paiardini Chapter 9 Immunotherapies and Vaccines 229 Hermancia S. Eugene and Ted M. Ross Chapter 10 HIV Envelope-Specific Antibody and Vaccine Efficacy 257 Egidio Brocca-Cofano, Peng Xiao and Marjorie Robert-Guroff Chapter 11 Role of Cytokines and Chemokines in HIV Infection 281 Vishwanath Venketaraman, Devin Morris, Clare Donohou, Andrea Sipin, Steven Kung, Hyoung Oh, Mesharee Franklin, John P. Murad, Fadi T. Khasawneh, Beatrice Saviola, Timothy Guilford and Clare Donahue Chapter 12 The Role of Genetic Polymorphisms in the Chemokine and their Receptors and Cytokines in the Human Immunodeficiency Virus Type 1 (HIV-1) Infection 301 Edna Maria Vissoci Reiche, Marla Karine Amarante and Maria Angelica Ehara Watanabe Chapter 13 CXCL8 Regulation and Function in HIV Infections and Potential Treatment Strategies 327 Per-Erik Olsson, Hazem Khalaf and Jana Jass Chapter 14 Emerging Roles of Prostaglandins in HIV-1 Transcription 345 Nancy Dumais, Sandra C. Côté and Anne-Marie Ducharme Part 3 From the Clinic to the Patients: HIV and Clinical Manifestations 371 Chapter 15 Pathology of HIV/AIDS: Lessons from Autopsy Series 373 Andrey Bychkov, Shunichi Yamashita and Alexander Dorosevich Chapter 16 HIV and Lung Cancer 393 Yusuke Okuma, Naoki Yanagisawa, Yukio Hosomi, Atsushi Ajisawa and Masahiko Shibuya Chapter 17 Neuropsychiatric Manifestations of HIV Infection and AIDS 415 Victor Obiajulu Olisah Contents VII Chapter 18 AIDS and Trauma 443 Erik Vakil, Caroline Zabiegaj-Zwick and AB (Sebastian) van As Chapter 19 Cutaneous Manifestations of HIV/AIDS in Sub-Sahara African 453 Innocent Ocheyana George and Dasetima Dandison Altraide Chapter 20 Benign and Malignant Lymphoproliferative Disorders in HIV/AIDS 463 Etienne Mahe and Monalisa Sur Chapter 21 Sexual Dysfunctions 503 Marco de Tubino Scanavino Chapter 22 AIDS Changed America with the Twin Breast Cancer Epidemic: Exploring the Consequences of Condomization 519 Arne N. Gjorgov Part 4 From the Clinic to the Patients: Transmission, Diagnosis and Therapies 581 Chapter 23 Transmission of HIV Through Blood – How To Bridge the Knowledge Gap 583 Smit Sibinga, Cees Th and John P. Pitman Chapter 24 Molecular Epidemiology of HIV-1 Infection in the Amazon Region 619 Antonio Carlos Rosário Vallinoto, Luiz Fernando Almeida Machado, Marluísa de Oliveira Guimarães Ishak and Ricardo Ishak Chapter 25 Saliva Testing as a Practical Tool for Rapid HIV Screening 627 H. Blake, P. Leighton and S. Sharma Chapter 26 HAART and Causes of Death in Perinatally HIV-1-Infected Children 641 Claudia Palladino, Jose María Bellón, Francisco J. Climent, María del Palacio Tamarit, Isabel de José and Mª Ángeles Muñoz-Fernández Chapter 27 Cannabinoids – Influence on the Immune System and Their Potencial Use in Supplementary Therapy of HIV/AIDS 665 Alicja Szulakowska and Halina Milnerowicz Chapter 28 Small Livestock, Food Security, Nutrition Security and HIV/AIDS Mitigation 681 John Cassius Moreki and Richard Dikeme Preface The ongoing research efforts that started even before our recognition of the HIV/AIDS syndrome and identification of HIV as the causative agent have made important inroads into our knowledge and understanding of this terrible disease. Nevertheless, the continuing AIDS pandemic and profound human and socio-economic impacts remind us that despite the unrelenting quest for knowledge since the early 1980s, we have much to learn about HIV and AIDS. Moreover, the copious amount of research performed on HIV and AIDS requires comprehensive overviews on this subject in order to provide clues and opportunities for future research. With this in mind, the purpose of this book is to aid clinicians, provide a source of inspiration for researchers, and serve as a guide for graduate and medical students in their continued search for an understanding and finally, a cure of HIV. This volume has four sections grouped in two parts. The first part, “From the laboratory to the clinic,” and the second part, “From the clinic to the patients,” represent the unique but intertwined mission of this work: to provide basic and clinical knowledge on HIV/AIDS. The first two sections describe how basic research generates knowledge that impacts clinical practices. The first section details the multifaceted interactions that occur between HIV and host cells. Functions of the accessory protein Nef during the lentivirus replication cycle are reviewed in Chapter 1. Chapter 2 explains how HIV-1 proteins and therapeutic antiretroviral drugs cause oxidative stress-induced cardiovascular disease and neurological disorders. Chapter 3 is a comprehensive update on the prevalence of multiple HIV-1 subtypes, and how this influences pathogenesis, evasion on the immune system, and vaccine development. Insulin-like growth factor (IGF) levels are closely monitored in HIV/AIDS patients and help track the progression of the disease and Chapter 4 provides structural information on IGF and explains how understanding the IGF system may be useful for developing potent therapeutics. The information of Chapters 5 and 6 is presented to better understand the interactions between HIV and cellular proteins and the development of intrinsic immunity. These chapters discuss how host proteins are capable of inhibiting HIV-1 replication. These host proteins, termed cellular restriction factors, are a new and important research area that may provide new avenues for AIDS therapies. X Preface The second section focuses on the relationship between HIV and the immune system. Continued study of the persistent HIV animal reservoir may provide insight into new vaccine strategies or therapeutic approaches for the treatment of HIV-infected humans. This very important area of HIV research is reviewed in Chapter 7. Chapters 8 and 9 approach some fundamental principles behind the design and development of effective vaccines and/or immunotherapies. These chapters are followed by a series of chapters (Chapter 10 to Chapter 13) that provide information on the role of cytokines, chemokines, and prostaglandins in HIV infection and pathogenesis. The second part of this book is a compendium of chapters dedicated to AIDS and HIV epidemiology and clinical research. The third section entitled “HIV/AIDS and clinical manifestations” describes clinical manifestations of HIV/AIDS. Postmortem examinations provide important diagnostic and epidemiological data on the myriad diseases associated with HIV infection. Chapter 14 presents data from post-mortem surveillance from 1982 to 2011 showing differences in HIV epidemiology in Africa, Asia, the U.S., and Europe. Chapter 15 discusses the epidemiology, frequency, risk factors, clinical management, and treatment of HIV-infected lung cancer patients. Neuropsychiatric manifestations of HIV infection and AIDS are presented in Chapter 16. Chapter 17 presents information related to the treatment of HIV/AIDS patients in trauma units, an area of study that has been neglected. The aim of Chapter 18 is to highlight common cutaneous manifestations of HIV/AIDS in sub-Sahara Africa. Chapter 19 explores a number of the many possible HIV/AIDS associated disorders of the lymphoid system. Chapter 20 investigates the etiologic factors involved in the sexual dysfunctions of HIV/AIDS patients, proposes steps for assessment and diagnosis, and recommends therapeutic strategies for these patients. Chapter 21 explores consequences of condomization of women’s sexuality on female diseases and dysfunctions. Several aspects of two devastating epidemics, breast cancer and AIDS, are discussed in this chapter. The final set of chapters presented in the fourth section offers scientific data on epidemiology, transmission, diagnosis, and therapies for HIV. Lack of education increases the risk of HIV transmission and Chapter 22 gives strategies to better understand transmission of HIV through blood. Chapter 23 focuses on molecular epidemiology of HIV-1 infection in the Amazon region, while Chapter 24 presents data on HIV/AIDS in Nigeria. Methods for saliva testing for HIV screening are described in Chapter 25. In Chapter 26 examines paediatric HIV infection risk factors, causes of death, and the impact of HAART in HIV-1 infected children. The effect of nutritional status among persons with HIV and drug addictions is explored in Chapter 27. Chapter 28 reviews the influence of cannabinoids on the immune system and their potential use in supplementary therapy for HIV/AIDS, as well as the importance of food and nutrition security in the mitigation of HIV/AIDS in sub- Saharan Africa. [...]... step of the viral replication cycle Several studies reported that HIV- 1 Nef expression alters the lipid composition of virions by increasing cholesterol biosynthesis and its incorporation into 18 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies DRMs, therefore Nef increases the concentration of Gag and colocalizes with viral structural components in the DRMs These... interacts and prompts the degradation of a family of cytidine deaminases DNA/RNA editing enzymes, known as Apoliprotein B mRNA-editing Enzymes (APOBECs), that otherwise would inhibit HIV and SIV replication by causing hypermutation of nascent 4 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies retroviral genomes by deamination of cytidine residues (Aguiar and Peterlin,... responsible for the interaction with the ESCRT-I component, Tsg101; PPxY, that engage 20 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies interactions with the Nedd4 ubiquitin ligase family; and YPxL, that interact with Alix/AIP-1 (Freed and Mouland, 2006) The fact that these late domains maintain its functionality even when translocated to other regions of viral proteins... SIVwrc, SIVgri, SIVlho, and SIVasc downmodulated TCR/CD3 efficiently (Schindler et al., 2006; Schmokel et al., 2011) 12 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies In a previous report, an association between Nef proteins of all vpu-containing viruses and the loss of ability to down-modulate the TCR/CD3 was demonstrated, hence only vpucontaining viruses were... (Marbuburg, Ebola), and herpesviruses (KSHV) (Mansouri et al., 2009) Tetherin belongs to the three main classes of restriction factors in addition to 14 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies APOBEC3G, which induces hypermutation in the retroviral genome, and the Tripartide Motif Protein 5α (TRIM 5α), which acts as new incoming retroviral capsid restriction factor... viral infectivity are listed on Table 22 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies 1 From this data we can observe that most of the mutations that prevented cleavage correlated with a reduction in viral infectivity, however some mutations that still allow cleavage to happen also had an impact on viral infectivity Based on these observations authors excluded that... components needed to Ii degradation and foreign peptide loading onto the MHC-II cleft The mature MHC-II is then directed to the cell membrane where interaction with the TCR of a CD4+ cell can happen A fraction of immature MHC-II travels to the plasma membrane and is subsequently 8 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies internalized and directed to MIIC vesicles... Distinct Steps of HIV and SIV Replication Cycle 15 4 Nef and the basic steps of the HIV and SIV replication cycle 4.1 Nef and virus entry and uncoating HIV and SIV enter target cells by fusion of the viral envelope with the cell membrane followed by the delivery of the virion core inside the cell cytoplasm The host cell cytoskeleton imposes the first physical barrier to viral invasion upon entry and Retroviruses... on the cell membrane reduces the ability of the newly formed particles to be properly released from the 6 HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies infected cell therefore reducing viral infectivity (Cortes et al., 2002; Lama et al., 1999) Finally, decreasing the number of viral receptors on the surface of an infected cell seems to prevent reinfection by HIV/ SIV... downmodulation of mature and upregulation of immature MHC-II is a function conserved in many nef alleles from HIV- 1/2 and SIVs Contrary to what is seen in MHCI downmodulation, Nef activity on MHC-II and Ii do not change significantly during the stages of infection Of note, the strong Ii upregulation observed in the presence of wild type Nef is lost in some nef alleles derived from Long-term infected HIV- 1 . HIV AND AIDS – UPDATES ON BIOLOGY, IMMUNOLOGY, EPIDEMIOLOGY AND TREATMENT STRATEGIES Edited by Nancy Dumais HIV and AIDS – Updates on Biology, Immunology, Epidemiology. SIV replication by causing hypermutation of nascent HIV and AIDS – Updates on Biology, Immunology, Epidemiology and Treatment Strategies 4 retroviral genomes by deamination of cytidine. interaction with the TCR of a CD4+ cell can happen. A fraction of immature MHC-II travels to the plasma membrane and is subsequently HIV and AIDS – Updates on Biology, Immunology, Epidemiology and