1. Viral Infections: an overview Dr. Meg-angela Christi Amores

2. Defining a Virus Viruses consist of a nucleic acid surrounded by one or more proteins obligate intracellular parasites: they can replicate only within cells Many human viruses are simply composed of a core and a capsid Genes: contain either DNA or RNA

3. RNA VirusesDNA Viruses Picornaviruses Poliovirus Coxsackievirus Echovirus Enterovirus Rhinovirus Hepatitis A virus Herpesviridae Herpes simplex virus types 1 and 2 b Varicella-zoster virus c Epstein-Barr virus d Cytomegalovirus e Human herpesvirus 6 Human herpesvirus 7 Calciviridae Norwalk agent Hepatitis E virus Hepadnaviridae Hepatitis B virus Togaviridae Rubella virus Eastern equine encephalitis virus Western equine encephalitis virus Papovaviridae Human papillomaviruses JC virus BK virus Flaviviridae Yellow fever virus Dengue virus St. Louis encephalitis virus West Nile virus Hepatitis C virus Hepatitis G virus Poxviridae Variola (smallpox) virus Orf virus Molluscum contagiosum virus

4. RNA VirusesDNA Viruses Coronaviridae Coronaviruses Adenoviridae Human adenoviruses Rhabdoviridae Rabies virus Vesicular stomatitis virus Parvoviridae Parvovirus B19 Filoviridae Marburg virus Ebola virus Paramyxoviridae Parainfluenza virus Respiratory syncytial virus Newcastle disease virus Mumps virus Rubeola (measles) virus Orthomyxoviridae Influenza A, B, and C viruses Bunyaviridae Hantavirus California encephalitis virus Sandfly fever virus

7. Viral Infection Transmission – capsid and envelope of a virus protect its genome – Most common viral infections are spread by direct contact by ingestion of contaminated water or food by inhalation of aerosolized particles – Animals are important reservoirs and vectors for transmission of viruses causing human disease

8. Viral Infection Primary Infection – usually lasts from several days to several weeks enterovirus, mumps virus, measles virus, rubella virus, rotavirus, influenza virus, AAV, adenovirus, HSV, and VZV are cleared from almost all sites within 3–4 weeks AAV, EBV, or cytomegalovirus (CMV) can last for several months HBV, HCV, hepatitis D virus (HDV), HIV, HPV, and molluscum contagiosum virus extend beyond several weeks

9. Viral Infection Primary Infection – Disease manifestations usually arise as a consequence of viral replication and the resultant inflammatory response – are cleared by nonspecific innate and specific adaptive immune responses – host is usually immune to the disease manifestations of reinfection by the same virus

10. Persistent and Latent Infections – HCV RNA polymerase and HIV reverse transcriptase have high mutation rates – generation of variant genomes that evade the host immune response facilitates persistent infection – DNA viruses: lower mutation rates ability to establish latent infection and to reactivate from latency

11. Persistent and Latent Infections latency is defined as a state of infection in which the virus is not replicating HPVs establish latent infection in basal epithelial cells

12. Persistent and Latent Infections Herpesviruses: latent infection is established – in nonreplicating neural cells (HSV and VZV) – in replicating cells of hematopoietic lineages [EBV and probably CMV, HHV-6, HHV-7, and Kaposi's sarcoma–associated herpesvirus (KSHV, also known as HHV-8)].

13. Persistent Viral infections and Cancer – estimated to be the root cause of as many as 20% of human malignancies – Most hepatocellular carcinoma is now believed to be caused by chronic inflammatory, immune, and regenerative responses to HBV or HCV infection – Almost all cervical carcinoma is caused by persistent infection with "high-risk" genital HPV strains – EBV infection also plays a role in the long-term development of certain B lymphocyte and epithelial cell malignancies

14. Resistance to Viral Infections Initial response is not virus-specific Physical – cornified layers of the skin and by mucous secretions that continuously sweep over mucosal surfaces Cellular – IFNs are induced and confer resistance – cytokines may be chemotactic to inflammatory and immune cells

15. Resistance to Viral Infections By 7–10 days after infection, virus-specific antibody responses develop virus-specific HLA class II–restricted CD4+ helper T lymphocyte responses, and virus-specific HLA class I– restricted CD8+ cytotoxic T lymphocyte responses Antibody and complement can also lyse virus-infected cells that express viral proteins on their surface

16. host inflammatory and immune response contributes to the symptoms, signs, and other pathophysiologic manifestations of viral infection

17. Diagnostic Virology Serology Viral Isolation Acute- and convalescent-phase sera with rising titers of antibody to virus-specific antigens shift from IgM to IgG antibodies

18. Diagnostic Virology ELISA (Enyme-Linked Immunosorbent Assay) – generally use specific viral proteins that are most frequently targeted by the antibody response – amount of antibody can then be quantitated by the intensity of a color reaction mediated by the linked enzyme

19. Virus isolation – depends on the collection of specimens from the appropriate site – the rapid transport of these specimens in the appropriate medium to the virology laboratory – Rapid transport maintains viral viability and limits bacterial and fungal overgrowth.

20. Treatment Multiple steps in the viral life cycle can be effectively targeted by antiviral drugs – synthesis of the HIV provirus – block maturation of the HIV polyprotein – preventing a conformational change required for virus fusion – preventing release of viral RNA early during infection – Prevent efficient release of mature virions

21. Immunization Smallpox Poliovirus Measles Influenza Chickenpox HBV Mumps, rubella