Virology Primer
Viruses have no metabolism and no protein synthesis machinery. They rely on entering living hosts and de novo assembly of new infectious particles.
Virus Particle
Payload
Can be DNA or RNA.
Most small genomes rely on host DNA copying enzymes. Large genomes require more complex replication and host immune avoidance strategies.
In RNA genomes, the virus contains their own RNA-dependent RNA polymerase (which humans do not have) and uses a protease to produce viral proteins. The polymerase has low-proofreading activity which results in more mutations and better immune avoidance/drug-resistance.
Naked capsids
Protein only. They are environmentally stable, infectious even when dried, and resistant to detergents. Most will kill the infected cell to release progeny.
Antibodies are sufficient for immunoprotection. Vaccination with a killed virus is often effective.
Enveloped capsids
Protein plus a lipid bilayer. They are environmentally labile, must remain wet, and are disrupted by detergents. They spread in droplets, secretions, and transfusions. The virus fuses with the cell membrane to enter. New viruses are released from the cell by budding or lysis. Those which don't kill the cell can exist chronically.
Require cell mediated immune response for elimination.
Pathogenesis
Attachment is the biggest determining factor of cell type specificity. The route of entry is determined by physical properties, site of replication, and type of infection.
Symptoms can depend on direct effects of virus on infected cells or inflammatory responses to the virus. Local infections occur near where the virus enters the body (e.g., respiratory syncytial virus). Systemic infections infect target tissues elsewhere in body via the bloodstream, lymphatic system, or nervous system.
- Cytopathic effects (CPE): Morphological changes in host cells, including lysis, syncytia, an inclusion bodies
- Replication with no apparent effect: e.g., HBV, HCV
- Latent infection: No active production of infectious viral particles. These viruses can be activated at a later point.
- Tumorigenesis: Direct manipulation of host cell division mechanisms or a combination of environmental, viral, and host genetic factors
Acute infections
Resolves in days to weeks. Antibodies used for naked capsids and CD8 cells for enveloped capsids. Reinfection is determined by variations in virus sequence or persistence of immune response.
Chronic infections
In which the virus remains in the body. In these cases the immune system fails to get rid of it and carries the potential for chronic or intermittent illness.
Lab Techniques
Detection of virus genome (PCR)
- Highly sensitive and specific
- Requires appropriate samples
- Limited by availability
Detection of virus proteins (antigens)
- Rapid diagnostic test (RDT): Delivered at point of care, but less sensitive
- Requires less appropriate samples
Detection of anti-virus antibodies
- Requires blood samples
- Antibodies detectable for long time, but are only formed after two weeks
- High fast positive rate
Histological markers
- Requires appropriate sample
- Looks for inclusion bodies/syncytia
Virus growth in culture
- Sensitive
- Slow process
- Some viruses can't be grown
Anti-Viral Therapy
Immune system modulation (indirect)
Supports the immune system’s response through use of interferons (primarily interferon alpha). Has poor efficacy and side effects from cytokines.
Direct-acting antivirals (DAA)
Targets specific virus replication steps. Available for only a few viruses (HIV, HCV, HBV, Influenza, Herpes viruses, SARS CoV-2).
There are no highly effective broad-spectrum antivirals as replication mechanisms are too varied and target proteins too dissimilar.