Viral Receptors & Entry Flashcards
What is the difference between a permissive and susceptible cell?
- Permissive = virus can enter and replicate
- Susceptible = virus can enter but not replicate
What are the 3 levels of viral tropism?
- Host
- Tissue
- Cellular
What does viral entry define?
Tropism and pathogenicity.
If a virus can’t enter a cell, it can’t do anything- obligate intracellular parasites
What are the 3 determining factors of viral tropism?
- Presence of correct receptor
- Permissive intracellular environment
- Accessibility
What is the attachment mechanism of non-enveloped viruses?
Capsid proteins (like spike proteins) interact directly with receptors
What is the attachment mechanism for enveloped viruses?
Glycoproteins embedded in lipid bilayer bind to receptors
What are attachment factors?
Help concentrate the virus on the cell surface via weak, non-specific interactions
What is the receptor for HIV?
CD4 w coreceptor CCR5/CXCR4
What is the receptor for Influenza?
Sialic acid (broad receptor in humans but Influenza infects lungs preferentially)
How does Influenza enter cells?
Through clathrin-mediated endocytosis.
Formation of clathrin-coated pits that invaginate and form vesicles
What is macropinocytosis?
Cells engulf extracellular fluid and viruses into large vesicles (called macropinosomes).
Non-specific uptake mechanism- suitable for larger viruses
What is the advantage of viruses hijacking endocytosis?
- Shielded inside the vesicle from immune sensors
- Leaves no immediate trace of entry at the plasma membrane
What are the 3 main sites of uncoating?
- Plasma membrane (outer)
- Endosome
- Nuclear membrane
Where does HIV uncoat?
At the plasma membrane (direct fusion -> genome release)
What is the purpose of uncoating?
Removes protective layer (capsid/envelope) and exposes viral genome for transcription and replication
Where does Influenza uncoat?
At the endosomal membrane (fusion following acidification of maturing endosomes)
What are fusion proteins?
Viral proteins that catalyse the merging of viral and host membranes
What are some features of fusion proteins?
- Trigger structural rearrangements necessary for genome delivery
- Typically metastable
What does metastable mean wrt fusion proteins?
Spring-loaded to change shape (to allow fusion) when triggered (e.g. by endosome pH drop in Influenza)
What class is the fusion proteins used by Influenza and HIV?
Class I (alpha helices)
What is the fusion protein used by Influenza?
Haemagglutinin
What is the fusion protein used by HIV?
gp41
Why do fusion proteins make a good drug target?
Highly conserved among virus families
How do viruses that replicate in the nucleus cross the nuclear barrier?
They gain entry through nuclear pore complexes
