Viral Entry Flashcards
Is viral entry passive or active?
Active
What does the entry process facilitate?
Uncoating - helps virus get out of capsid
What are the receptors for viruses on host cells?
Typically glycoproteins (carb branches) on the outside of the cell
How do phagocytic cells take up viruses?
Particles are engulfed by the cell and extensions fuse around the particle. Phagosomes fuse with lysosomes and the particles are destroyed
What is the most important route of entry for viruses?
RME
What is the process of RME?
- Ligand binds a cell surface receptor. This diffuses into an invagination coated with clathrin
- The clathrin pit pinches off forming a coated vesicle
- The clathrin uncoats the vesicle
- The vesicle fuses with an early endsome which is acidic
- The acidification releases the ligand from the receptor, and the receptor is returned to the cell surface
How are rhinovirus and poliovirus related?
They are both picornaviruses (RNA viruses)
They both use proteins on the host cell as receptors
What is the receptor for polio and what is it involved in?
Pvr
Involved in DC-NK interactions
What is the receptor for rhinovirus and what is it involved in?
Icam-1
Icam-1 is involved in macrophage T-cell interactions
What do rhinoviruses cause?
The common cold >90 serotypes
What does the presence of the receptor determine?
Specificity of the viruses host range
How does rhinovirus enter the cell?
The virus attaches to Icam-1 and enters by endocytosis
The acidic environment of the endosome causes the uncoating of the particle and the RNA is released into the cytoplasm
What does Icam-1 deep in canyon facilitate?
Destabilization of the capsid - there is a direct interaction between receptor and capsid
What is rhinovirus not resistant to?
Acid
Why is it significant that the receptor binding site (Icam-1) is recessed?
Because the receptor interaction site is inaccessible to antibodies
What do neutralizing antibodies do?
Blocks the binding of the receptor to the canyon
Where does rhinovirus bind on Icam-1?
D1
What binding site does HRV overlap with?
LFA-1
How does polio enter the cell?
Pvr interaction causes major structural changes - enters by RME
The N termini of the VP1 protein extends into the membrane which may fore a pore in which RNA can enter
What doesn’t Fc-receptor-mediated internalization of polio allow?
Uncoating
What is polio resistant to?
Acid
How does influenza enter the cell?
It is an enveloped virus so it undergoes membrane fusion which is a regulated process involving proteins for targeting and docking
What do enveloped viruses encode?
Fusogens which facilitate membranes to join together
What is the receptor for influenza attachment?
Sialic acid = integral membrane glycoprotein
What does influenza virus hemagglutinin bind to?
Terminal sialic acid
Which linkage of sialic acid does avian HA prefer?
alpha 2-3 glycosidic linkage
Which linkage of sialic acid does human influenza HA prefer?
alpha 2-6 glycosidic linkage
How does influenza enter the cell using hemagglutinin fusogen?
Fusogenic peptide is exposed by an acid-catalyzed structural change
The virus RNA is in two membranes and it uses its fusogen to get out
The acidic environment of the endosome causes conformational change in HA
When is HA activated?
When cleaved into HA1 and HA2
What is the most important part of the influenza virus?
The fusogen and it is kept hidden until it is used
Which receptor does SARS-CoV2 use for cell entry?
ACE2, binds to the spike protein
