Lecture 34. Virus Replication Cycle 1 Flashcards
What is the cytopathic effect ?
Cell to cell spread of virus resulting in plaque formation
How can the cytopathic effect be useful to scientists ?
A way to count viruses - plaque assay
What is the assumption of counting the cytopathic effect ?
Each plaque begins with 1 virus particle
How does the cytopathic effect contribute to HIV ?
- Infects CD4+ T-cells
2. Constant destruction of T-cells
How does the cytopathic effect contribute to poliovirus ?
- Leads to gut and central nervous system infection
2. Muscle weakness
What is a susceptible cell ?
A cell which has a functional receptor for a given virus, allowing the virus to enter the cell (the cell may or may not be able to support virus replication)
What is a resistant cell ?
Has no receptor (the cell may or may not be able to support virus replication)
What is a permissive cell ?
Has the capacity to support virus replication (may or may not be susceptible)
Where can a virus enter and replicate ?
In a cell that is both susceptible and permissive
What are initial collisions between virions and cells governed by ?
Chance
Do virions have powers of locomotion ?
No, they are inanimate
How is virus movement driven ?
Brownian motion, diffusion, electrostatic interactions
What are the two steps of attachment ?
- Adherence to cell surface
2. Attachment to specific receptor molecules on the cell surface
How do virions attach to the cell surface ?
- Electrostatic interactions
2. Non-specific interactions
What type of interactions occur between virions and receptors on cell surface ?
Specific and specialised
How many receptors can be involved in virions attaching to receptors on cell surface ?
More than one
Can different virus bind to the same receptor ?
Yes
Can virus bind to more than one type of receptor ?
Yes
What is the poliovirus receptor ?
CD155
What is CD155 ?
Cellular adhesion protein
What superfamily is CD155 from ?
Immunoglobulin
Where is CD155 expressed ?
- Endothelial cells
2. Immune cells
How does CD155 interact with poliovirus ?
By the viral capsid
What is the influenza virus receptor ?
Sialic acid
What is sialic acid ?
Small sugar modification attached to the many different proteins on the cell surface
Where is sialic acid expressed ?
Respiratory endothelium
How does sialic acid interact with the influenza virus ?
Viral Hemagglutinin Protein (Ha)
What is the HIV receptor ?
CD4
What is the HIV receptor superfamily ?
Immunoglobulin
What is CD4’s co-receptor ?
CCR5 or CXCR4
Where is CD4 expressed ?
CD4 positive T-cells
Where doe the HIV virus interact with the virus ?
Viral gp120 and gp41 proteins
What is varicella zoster virus receptor ?
Heparin sulfate proteoglycans
What is varicella zoster virus cellular tropism ?
- Mucosal epithelia - upper respiratory tract
- Lymphoid tissue
- Skin
- Latent infection - ganglionic neurons
Where does varicella zoster virus receptor interact with virus ?
Viral gB protein
What is SARS-CoV-2 receptor ?
Angiotensin converting enzyme (ACE2)
Where is the ACE2 receptor expressed ?
Broad distribution- epithelial respiratory cells
Where does ACE2 receptor interact with the virus ?
Viral spike protein
What does receptor specificity determine ?
Susceptibility of cells
How do cells internalise things from outside the cell ?
- Phagocytosis
2. Endocytosis
How does HIV enter the cells ?
Fusion at the plasma membrane
What are the 4 ways viruses enter cells ?
- Clathrin dependent endocytosis
- Clathrin/caveolin independent endocytosis
- Caveolin dependent endocytosis
- Fusion at the plasma membrane
What is the HIV entry to the cell process?
A pH independent process
What does interaction between viral proteins and cellular receptors trigger in HIV ?
Conformational change in viral proteins
What are the two conformational changes in viral proteins in HIV ?
- Change in gp120 promotes binding to chemokine receptor
2. Change in gp41 exposes fusion peptide, which inserts into T-cell membrane
What does the conformation change mediate ?
Membrane fusion
How does influenza enter the cells ?
Low pH dependent receptor mediated endocytosis
What triggers conformational change in Hemagglutinin (HA) viral protein in influenza entry ?
Acidification of endosomes
How do non-enveloped viruses (poliovirsu) enter cells
Receptor dependent conformational change of virion creates a pore in endosomal membrane
What forms the pore in the endosomal membrane in poliovirus ?
VP1
What is the model of genome uncoating ?
- Virion binds to receptor
- Conformational change - VP1 inserted into plasma membrane
- A pore is formed in the membrane by VP1, the RNA genome is released into cytosol
How does SARS-CoV-2 enter the cell ?
Receptor mediated endocytosis
What cuts the viral spike protein in SARS-CoV-2 in specific places ?
TMPRSS2
What does the conformational change in the spike protein in SARS-CoV-2 result in ?
The spike protein becoming embedded in the endosomal vesicle membrane