Attachment & Entry Flashcards
What is the criteria to identify receptors for viruses?
Loss of function
- disruption of receptor gene blocks infection
Gain of function
- Receptor gene confers susceptible
Antibody specific to receptor blocks infection
What is essential for coronavirus (MERS) infection?
Dipeptidyl peptidase 4 (DPP4)
Where is DPP4 expressed?
Lung and kidney cells
What are types of cleavage enzymes?
Growth factors, chemokines, neuropeptides, vasoactive peptides
What is an “Natural” Plasmid?
Origin of Replication
Advantageous gene
What is a “Artificial” Plasmid?
Origin of replication
Selectable marker
Cloning site
- insert gene of interest (GOI)
Which plasmid is usually used for scientists?
“Artificial” plasmids
What is a plasmid?
Small circular piece of DNA that replicates independently from the host’s chromosomal DNA
Where are plasmids mainly found?
Bacteria
What are plasmids also known as?
Vector
Construct (artificial plasmids)
How do non-enveloped viruses interact with receptors?
Bind via projections
Protein-protein interaction
How do enveloped viruses (HIV) interact with receptors?
Bind via transmembrane glycoproteins
protein-protein interaction (because both are proteins)
How do enveloped viruses (Influenza) interact with receptors?
Bind via transmembrane glycoproteins
protein-carbohydrate interaction
What is the reasoning for the name glycoproteins?
Lots of sugar and molecules in them
What makes the influenza virus different from HIV?
the interaction
- protein-protein (HIV)
- protein-carbohydrate (Flu)
Influenza has a HA (hemagglutinin) trimer and NA (neuraminidase) tetramer
What recognizes the bondage of the terminal sialic acid and galactose in the host cell?
Viral envelope protein HA (hemagglutinin)
What type of linkages bond the terminal sialic acid and galactose?
a(2,6) linkages for humans
a(2,4) linkages for birds
both linkages present in pigs
Why does HA binding affinity and NA activity need to be balanced?
For efficient viral entry and release
What happens if HA binding affinity > NA activity?
Trapped binding
- blocked/inefficient entry/release
What happens if NA activity > HA binding affinity?
Inefficient receptor binding
How does HIV-1 enter the cell?
Fusion at the plasma membrane
How is fusion regulated in HIV?
conformational changes
binding to receptor
What is CD4?
HIV host receptor
What is CCR5/CXCR4?
HIV coreceptor
What is gp120 (trimer)?
Viral surface protein in HIV that interacts with CD4
What is gp41 (trimer)?
Viral transmembrane protein in HIV that mediates fusion
How does SARS-CoV-2 enter the cell?
Fusion at the plasma membrane
How is fusion regulated in SARS-CoV-2?
Conformational changes
Cleavage of viral glycoprotein
By host protein
How does dengue enter the cell?
Acid-catalyzed (Dengue)
Enter by endocytosis
- Clathrin-dependent endocytosis
How is fusion regulated in Dengue?
low pH
- conformational changes expose fusion peptide
How does Ebola enter the cell?
Membrane fusion
- Endosomal fusion receptor
Clathrin-dependent endocytosis
How is fusion regulated in Ebola?
Low pH
- GP cleavage
GP binds to fusion receptor - Niemann-Pick C1 protein - Niemann-Pick type C1 disease - Patient cells resistant to Ebola virus infection (mutation in cell)
How do non-enveloped viruses enter and move within cells?
Disruption of endosomal membrane
Forming a pore in the endosomal membrane
How does Adenovirus enter cells?
Disruption of endosomal membrane
Adenovirus is non-enveloped
Clathrin-dependent endocytosis
How is fusion regulated in Adenovirus?
Low pH
- capsid destabilization, release of proteins
- destabilize endosomal membrane
How does Poliovirus enter cells?
Forming a pore in the endosomal membrane
Poliovirus is non-enveloped
Clathrin-dependent endocytosis
How is fusion regulated in poliovirus?
Conformational rearrangements
- VP1/VP4 = interior to exterior capsid surface
- Formation of pore
What are the big changes between enveloped viruses and non-enveloped viruses?
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