Viral Infections: an overview

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

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 molluscumcontagiosum 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