Diagnosis of viral infections Introduction to Virology Dr Kevin Forward R 315 Mackenzie Bldg 5788 University Ave 473 4109 kevin forward@cdha nshea lth ca A virus is A package of genetic information pr[.]
Introduction to Virology Dr Kevin Forward R 315 Mackenzie Bldg 5788 University Ave 473-4109 kevin.forward@cdha.nshea A virus is: A package of genetic information protected by a protein shell for delivery into a host cell to be expressed and replicated "Virus" is from the Greek meaning for "poison“ and was initially described by Edward Jenner in 1798 Viruses as distinct groups of infectious agents • Characteristics which differentiate viruses from other microorganisms – Nucleic acid (DNA or RNA) – Lack of nuclear membrane and external cell wall – They have very small genomes, produce limited numbers of proteins and not possess many intracellular systems ie they are parasites > intracellular replication History of viral diseases Pock marks indicative of smallpox 1500 BC: Leg deformities indicative of poliomyelitis Viral diseases have played a major role in human history over whatever time scale we choose to explore: Over the past 1000 years: Smallpox and measles Over the past 100 years: Spanish flu, HIV Over the past 10 years: West Nile, SARS, Avian Flu Virus naming and classification Usually based on data available at the time of discovery: • Disease they are associated with – HIV, Measles • Cytopathology they cause – Cytomegalovirus • Site of isolation – Adenovirus, Enterovirus, Rhinovirus • Places discovered or people that discovered them – Epstein-Barr virus, West Nile Fever • Biochemical features – Retrovirus RSV Viral taxonomy • Viral classification is based upon: – Shape – Type and form of nucleic acid – Enveloped or naked – Mode of replication – Organization of the genome and antigenic differences Rotavirus Genomic organization Viral nucleic acids • RNA viruses – RNA single stranded • positive polarity • negative polarity – RNA double stranded • one piece • segmented • DNA viruses – single stranded – double stranded Viral structure • Capsomeres are structural subunits containing several proteins • Capsomeres aggregate to produce the viral capsid • The viral capsid associates with the viral nucleic acid to produce a nucleocapsid • Nucleocapsids are usually arranged in one of three ways – cubic, eg icosahedral (Herpes viruses) – helical (Influenza viruses) – complex Viral structure (cont’d) • Lipid envelopes are derived from cellular membranes • Studded with surface projections: (spikes or peplomers) • These are usually glysosylated by host systems prior to make them “sticky” How are viruses classified ? Hierarchical virus classification: Order- Family - subfamily genus - species - strain/type All families have the suffix viridae, e.g Herpesviridae Genera have the suffix virus For instance Coxsackie virus Examples to show differences in size and form Figure 16.10 Some representative DNA viruses DNA Icosahedral Naked Papilloma Parvovirus Adenoviruses Complex Enveloped Herpes viruses Hepatitis B Cytomegalovirus Herpes simplex and Varicella Zoster Epstein Barr Virus HHV 6-8 Pox viruses Some representative RNA viruses How you acquire these viral infections? • Direct personal contact – Herpes viruses, HIV, Influenza • Airborne spread – Chicken pox • Parenteral – HIV, Hepatitis B and C, cytomegalovirus (CMV) • Fomites – Enteroviruses and other sturdy drying resistant viruses • Vectors – West Nile • Vertical transmission – HIV, Herpes simplex, cytomegalovirus, rubella (German measles) • Enteral (foodborne) – Hepatitis A, gastroenteritis viruses Attachment Uncoating Replication Egress Assembly Virus adheres to specific receptors on susceptible cells Viruses are internalized by the cell, enter the cytoplasm Uncoating occurs, nucleocapsid is degraded by cellular proteases releasing nucleic acids (DNA or RNA) DNA may move to the nucleus, replication begins DNA > RNA RNA > RNA >RNA RNA > DNA >RNA Some proteins are processed further (glyosylated) Viral assembly occurs Virus exits cell by budding of lysis Consequences of virus-cell interaction • Viral proliferation and cell lysis – Cold sores, genital herpes,chicken pox • Latent infection (non replicating virus) – Most Herpes viruses, Human papilloma viruses – Viral genome may be integrated or not • Persistent infection (ongoing viral replication, few or no symptoms) – Hepatitis C and B, HIV – Tissue injury may be induced by the virus or the immune response to the viral infection • Oncogenesis (cellular proliferation) – Human papilloma virus, EBV • No apparent disease – eg Hepatitis G Diagnosis of viral infections • Clinical features typical of infection • Laboratory diagnosis – Histology and cytology – Direct examination by electron microscopy – Examination looking for viral antigens • In tissue • In serum – Antibody testing (rising IgG, IgM, very high titer IgG, any IgG) – Virus isolation – DNA or RNA amplification (in tissue sections, from tissue, in serum and fluids)