5 Pattern of Viral Infection Flashcards
Q: Define tropism.
A: The predilection of viruses to infect certain tissues and not others.
tropism of a virus is the place where it replicates
Q: What defines the tropism of a virus?
A: Susceptibility - receptor interactions
Permissivity - ability to use the host cell to complete replication
Accessibility - ability of the virus to reach the tissue
extracellular factors required for activation of virus infectivity
Q: Explain how the tropism of HIV is determined by receptor use.
A: Primary receptor is CD4 so HIV infects T cells
The gp120 on HIV interacts with CD4 on the T cell -> then attaches to a co-receptor (CCR5 or CXCR4)
Some people have mutation in CCR5 (delta 32) which means they don’t make a proper CCR5 receptor and hence are resistant to HIV
Some people who are exposed and unaffected produce a large amount of chemokine which blocks the use of the co-receptors
You can get a tropism switch during HIV replication - viruses evolve to bind to other receptors
Q: Explain how the tropism of the measles virus is determined by receptor use. What is the mechanism for the measles virus?
A: Has H receptor (hemagglutinin) which binds to: SLAM (CD155) and Nectin 4 at different stages
When infecting someone for the first time, measles enters via the respiratory tract -> Virus binds to SLAM on immune cells (e.g. dendritic cells) which are surveying the area -> they hijack a ride to the lymph nodes -> At the lymph nodes, the virus is exposed to more cells expressing SLAM which it then infects causing immunosuppression
When measles wants to leave the host and move on to another host, it uses NECTIN 4 -> Virus is carried from the lymph nodes to the lungs -> crosses from the blood to the airspace by binding to Nectin 4 which is on the bottom of the airway epithelial cells
Viruses replicate in airway epithelial cells and burst out into the airspace to spread via the respiratory route
Q: What are 2 examples of viruses whose tropism is determined by receptors?
A: measles, HIV
Q: Describe the tropism of influenza and its mechanism of action.
A: Influenza is enveloped in haemagglutinin (HA)
HA helps influenza latch onto the surface of cells by HA binding sialic acid which is UBIQUITOUS - it is everywhere so in theory, influenza can enter any cell of your body but only tends to affect the respiratory route - partly due to accessibility since Fusion with the membrane and uncoating can only happen if the protein of the virus has been snipped in two at a particular point - This requirement of cutting the protein into two pieces is what determines the tropism of the virus = It is only in the fluid that lines our lungs that the right proteases are present.
Influenza tropism is determined by availability of host proteases
it enters the cell via the endosome where Low endosomal pH allows a conformational change - essential for the virus to fuse with the endosome membrane and uncoat
Q: What is pathogenicity?
A: the ability of a virus to cause disease
Q: What is virulence?
A: described the capacity of a virus to cause disease
Q: What determines the outcome of virus infection?
A: balance between virus virulence and host response
Q: What is a viral rash?
A: If you have a systemic infection - blood can enter the skin and cause a rash. Can happen when virus leaves the blood and enters the skin
Q: Varicella Zoster Virus chicken pox: symptoms after secondary viraemia
A: Virus enters the body through the respiratory route
VZV can infect many cell types including peripheral blood mononuclear cells (PMBCs) and skin cells
From the skin site it can infect sensory neurones where it remains latent
Virus can be reactivated when cellular immunity is impaired causing a painful rash at nerve endings - SHINGLES
You only get symptoms after secondary viraemia
Q: What are the 4 patterns of viral infection?
A: Acute - followed by viral clearance
Persistent - latent, slow, transforming
Long incubations
Oncogenesis - affect the way our cells control themselves