Virus Entry

Question 1

What are the 3 stages involved in virus entry?

Answer 1

Attachment,
Penetration,
Uncoating

Question 2

What do viruses use receptors on the cell surface for?

Answer 2

Defining the cell tropism

Question 3

what are GAGs?

Answer 3

Glycosaminoglycans, polysaccharides on the surface of all cells, linear polysaccharides are linked or unlinked to cell surface proteins, negatively charged (sulphated) and bind viruses via electrostatic interactions

Question 4

What are the major and minor groups of receptors for Human Rhinovirus?

Answer 4

Major: Intracellular adhesion molecule-1 (ICAM-1) which is usually used for intracellular adhesion
Minor: Low density- Lipoprotein receptor which is usually used for the the uptake of lipids

Question 5

What does poliovirus bind?

Answer 5

CD155, normally functions in intracellular adhesion

Question 6

What is ICAM-1?

Answer 6

The HRV receptor, it binds into a cavity on the virus particle where antibodies cannot reach

Question 7

Which receptors much be present for a HIV infection to occur?

Answer 7

CD4 and chemokine receptors

Question 8

What is CD4?

Answer 8

CD4 has 4 extracellular IgG domains for binding to class II MHC on antigen presenting cells.

Question 9

What is a chemokine receptor?

Answer 9

E.g. CCR5 and CxCR4
7 transmembrane helices for binding chemokines. Early on in infection HIV infects macrophages bearing the B-chemokine receptor CCR5. Mutations in the V3 loop over time allow it to switch from acidic to basic amino acids so it an infect T-cells bearing the CxCR4 receptor.

Question 10

What does haemagglutinin bind?

Answer 10

A carbohydrate called sialic acid

Question 11

What does human haemagglutinin bind?

Answer 11

2,6 linkage to galagtose

Question 12

What does avian HA bind to?

Answer 12

2,3 linkage to galactose

Question 13

Give 5 cell surface proteins required for HCV entry

Answer 13

1. LDL
2. SR-B1
3. CD81
4. Claudin and Occulin receptor
5. EGF receptor (epidemal growth factor)

Question 14

What are the 3 mechanisms of endocytosis?

Answer 14

1. Clathrin mediated endocytosis
2. Non-clathrin dependent
3. Macropinocytosis

Question 15

What is clathrin mediated endocytosis?

Answer 15

Clathrin cage causes membrane curvature, this is then pinched off to form vesicles and targeted to the endosome which is acidified to release the contents

Question 16

What is non-clathrin dependent endocytosis?

Answer 16

Caveolae (lipid raft) forms invaginations in the plasma membrane. This is targeted to the ER.
Polyomaviruses and bunyaviruses

Question 17

What is macropinocytosis?

Answer 17

Membrane ruffling for large vesicles. Involved in fluid uptake.

Question 18

Give two methods of penetration of enveloped viruses?

Answer 18

1. Fusion of viral and endosomal membrane releases the capsid into the cytoplasm triggered by pH lowering. E.g. influenza
2. Fusion of viral and plasma membrane and the release of the capsid into the cytoplasm, e.g. HIV

Question 19

How does fusion occur?

Answer 19

Via a fusion peptide which is exposed by pH, co-receptor binding, K+ concentration and then causes a conformational change in the glycoproteins on the host cell membrane which it binds to. Causes the formation of a pore between the viral membrane and cellular membrane.

Question 20

What is the hemi-fusion intermediate?

Answer 20

When half of each plasma membrane is bound

Question 21

How do non-enveloped viruses penetrate?

Answer 21

Endocytosis followed by either:
1. Uncoating and endosome disruption,
2. Endosome disruption and uncoating 
3. Pore formation
Or receptor binding followed by:
1. membrane disruption 
2. Pore formation

Question 22

How does Influenza pass into the nucleus?

Answer 22

Through the nuclear pores, targeted by the ribonucleoprotein complex which is bound to the nucleic acids

Question 23

How does HIV pass into the nucleus?

Answer 23

Capsids are released into the cytoplasm, reverse transcription occurs and reverse transcription complexes pass along the microtubules to the nucleus using a targeting signal in the capsid.

Question 24

How does herpes access the nucleus?

Answer 24

Fuse at plamsa membrane releasing capsid and tegument proteins into the cytoplasm. Interaction with nuclear pore components allows the release of DNA and associated proteins into the nucleus.