Viral Infections: an overview

Dr. Meg-angela Christi Amores

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

RNA Viruses DNA Viruses

Picornaviruses Poliovirus Coxsackievirus Echovirus Enterovirus Rhinovirus Hepatitis A virus

Herpesviridae Herpes simplex virus types 1 and 2b

Varicella-zoster virusc Epstein-Barr virusd Cytomegaloviruse 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

RNA Viruses DNA Viruses

Coronaviridae Coronaviruses

Adenoviridae Human adenoviruses

Rhabdoviridae Rabies virus Vesicular stomatitis virus

Parvoviridae Parvovirus B19

Filoviridae Marburg virus Ebola virusParamyxoviridae Parainfluenza virus Respiratory syncytial virus Newcastle disease virus Mumps virus Rubeola (measles) virusOrthomyxoviridae Influenza A, B, and C virusesBunyaviridae Hantavirus California encephalitis virus Sandfly fever virus

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

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

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

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

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

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)].

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

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

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

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

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

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

• 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.

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

Immunization

• Smallpox• Poliovirus• Measles• Influenza• Chickenpox• HBV• Mumps, rubella