Lesson 1a: Mechanisms of viral infections

• Three requirements for ensuring a successful infection

1. Sufficient virus particles must be available
2. The cells at the primary site of infection must be accessible, susceptible, and permissive
3. The local host antiviral defense systems must be absent or at least initially defective

• There are several pathogenic mechanisms that must occur for a viral disease to develop:

1. Implantation of the virus at the portal of entry: Virions implant onto living cells mainly via the respiratory, gastrointestinal, skin-penetrating, and genital routes although other routes can be used. The final outcome of infection may be determined by the dose and location of the virus as well as its infectivity and virulence.
2. Local replication and local spread: Most virus types spread among cells extracellularly, but some may also spread intracellularly. Establishment of local infection may lead to localized disease and localized shedding of virus.
3. Dispersal/Spread to target organs (disease sites): The replicated viruses must spread to target organs (disease sites) throughout the body.Viremic: The most common route of systemic spread from the portal of entry is the circulation, which the virus reaches via the lymphatics. Virus may enter the target organs from the capillaries by (1) multiplying in endothelial cells or fixed macrophages, (2) diffusing through gaps, and (3) being carried in a migrating leukocyte.Neural: Dissemination via nerves usually occurs with rabies virus and sometimes with herpesvirus and poliovirus infections.
4. Replication in target Organs: Depending on the balance between virus and host defenses, virus multiplication in the target organ may be sufficient to cause disease and death.
5. Spread to sites of shedding of the virus into the environment: The viruses must spread to sites where shedding into the environment can occur. Although the respiratory tract, alimentary tract, urogenital tract and blood are the most frequent sites of shedding, diverse viruses may be shed at virtually every site.

• Factors that affect pathogenic mechanisms are

1. accessibility of virus to tissue,
2. cell susceptibility to virus multiplication, and
3. virus susceptibility to host defenses.

• Natural selection favours the dominance of low-virulence virus strains.

Incubation Period: The incubation period is the time between exposure to virus and onset of disease. During this usually asymptomatic period, implantation, local multiplication, and spread (for disseminated infections) occur.