Lec 5 - Virus attachment, entry and uncoating Flashcards
What 2 types of interactions are involved in binding of the host receptor?
- Reversible non-covalent binding
- Irreversible conformational changes
What is affinity?
The strength of binding
What is avidity?
The collective strength of all bonds
What is used to measure the strength of interaction and what is the typical value?
Dissociation constant K
1x10^-9
What type of cell does influenza A virus bind and how?
Epithelial cells of the upper respiratory tract. HA binds sialic acid and NA cleaves this bond for fusion
What is the type of sialic acid bound by human vs avian influenza strains?
Human: alpha-2,6-sialic acid
Avian: alpha-2,3-sialic acid
How does virus entry by pore formation work?
Virus binds receptors and injects genome through membrane via pore, leaving no spike proteins
How does virus entry by fusion work?
Virus binds receptors and fuses with cell membrane by its fusion peptide to release capsid into cell, leaving spike proteins on surface
How does clathrin mediated endocytosis work?
Virus enters clathrin coated pit and is endocytosed into vesicle. Acidification by vacuolar ATPase uncoats virus and clathrin is recycled
How does caveolae mediated endocytosis work?
Virus enters caveolae coated pit and is endocytosied into vesicle then taken to ER which requires dynamin. ER chaperone proteins uncoat virus
What is a 3rd method of endocytosis of viruses?
Phagocytosis by macrophages and neutrophils
How do picornaviruses eg poliovirus replicate in harsh environments eg human gut?
Poliovirus has a 4th protein subunit folded beneath the top 3 that’s only revealed after conformational change during binding
Where is the viral fusion peptide found?
Viral spike protein after conformational change
How does influenza release its genome?
- Fusion peptide to penetrate membrane
- Scission to split membrane
- Apposition to move membrane apart
- Hemifusion and pore formation
How does HIV release its genome?
- SU/gp120 binds CD4
- Conformational change so SU/gp120 binds CCR5 or CXCR4
- TM/gp41’s fusion pepide allows capsid to enter cell