Viral immune evasion Flashcards
What are 7 effects of antibodies on viruses?
- Antibody neutralises extracellular virus
- It blocks viral attachment proteins (e.g. glycoproteins, capsid proteins)
- It destabilises viral structure
- Antibody opsonizes virus for phagocytosis.
- Antibody promotes killing of target cell by the complement cascade and antibody-dependent cellular cytotoxicity.
- Antibody resolves lytic viral infections.
- Antibody blocks viremic spread to target tissue.
What antibodies are involved in viral infections?
IgM - indicator of recent or current infection
IgG - more effective antiviral than IgM
Secretory IgA - important for protecting mucosal surfaces
What are the 2 things resolution of a viral infection require?
- Elimination of free virus
2. Elimination of virus producing cells
How do rhinoviruses escape antibody recognition?
Human rhinoviruses exist as hundreds of antigenically distinct serotypes.
How does HIV escape antibody recognition?
HIV exists as multiple clades or quasi-species
How does Hep B virus (HBV) and ebola virus escape antibody recognition?
Encode secreted surface antigens that mop up antibody, stopping it reaching virus particles or infected cells.
How does dengue virus escape antibody recognition?
Exists as 4 serotypes. Previous infection with one serotype followed by infection with a different serotype can lead to antibody dependent enhancement of diseases as virus enters immune cells via antibodies and the Fc receptor. This triggers dengue hemorrhagic fever.
How does influenza virus escape antibody recognition?
Mutates each year by antigenic drift or can acquire completely new antigens by reassortment with animal viruses via antigenic shift.
What is the antiviral state?
Inferferons secreted by infected cells bind to interferon receptors that initiates the antiviral state. This involves the transcription of hundreds of genes that block viral replication for example 2,5 oligoadenylate synthetase and protein kinase R.
What are the 3 types of interferons?
Type 1 - Interferon alpha and beta. Interferon beta is secreted by all cells and interferon alpha receptors are present on all tissues. There is only one gene for interferon beta but 13-14 isotypes of interferon alpha. Plasmacytoid dendritic cells are specialised interferon alpha secreting cells.
Type 2 - Interferon gamma. Produced by activated T cells and NK cells. Signals through the interferon gamma receptor.
Type 3 - Interferon lambda. Signals through il28 receptors and interferon lambda receptors mainly present on epithelial surfaces.
How do viruses block the production of interferons?
Viruses like Hep B and influenza can block production of interferon by inhibition of interferon transcription. Influenza virus also produces a protein called NS1 that counters RNA sensing and prevents polyA processing (required to form mature mRNA).
What are some other ways viruses can evade the immune system?
- Antigenic variability
- Inhibition of phagocytosis or inhibition of phagosome-lysosome fusion.
- Viral latency (ability of a virus to lay dormant within a cell)
- Inhibition of antigen presentation