Lecture 11 - Herpes 1 Flashcards

1
Q

List 5 morphological features of Herpes viruses

A
  • Large viruses
  • linear dsDNA
  • icosahedral nucleocapsid
  • tegument proteins
  • enveloped
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2
Q

What is the role of the nucleocapsid portal vertex in Herpesviruses?

A

It is a hole for inserting DNA into the nucleocapsid during assembly. It closes after vDNA has been inserted into the nucleocapsid

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3
Q

What cell type do all herpesviruses initially infect?

A

Epithelial cells

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4
Q

What type of host cell surface receptors do herpesviruses bind to? What is the feature of the receptor that allows for binding to occur?

A

Glycosaminoglycans: they are sulfated sugars with a negative charge that allows the virus to bind to them

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5
Q

What are the 2 types of attachment Herpesviruses undergo in order?

A
  • initial attachment: reversible electrostatic interactions followed by
  • stable attachment: irreversible binding to receptor
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6
Q

What 2 ways can a Herpesvirus penetrate a cell?

A

-Membrane-envelope fusion
OR
-Receptor-mediated endocytosis

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7
Q

What are 2 reasons for studying virus receptors

A
  • Determining virus tropism

- Finding ways to interfere with virus attachment to host cells

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8
Q

Describe the steps in the Genetic Approach to finding a virus receptor

A

1) Start with a non-permissive cell type (one that the virus can’t infect and therefore doesn’t have a receptor for it)
2) Transfect non-permissive cells with genomic or cloned DNA from permissive cells. Some of the non-permissive cells will successfully transfect the DNA and express the receptor
3) Add recombinant virus virus carrying a drug-resistance gene to the transfected cells and select for with an antibiotic/cytotoxic drug. Only cells that were succesfully transfected would survive because they would express a receptor for the virus, absorb it and express drug resistance acquired from the virus.

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9
Q

Describe 3 ways you can check to see if cells transfected to express suspected virus receptors did in fact express the receptor, absorb virus and express vDNA?

A

1) add recombinant virus carrying drug resistance gene to cell culture - select for infected cells with antibiotics
2) add recombinant virus carrying an indicator gene to cell culture - only cells infected with virus will express indicator gene (ie. green fluorescence protein)
3) add fluorescently-labelled anti-receptor antibody - infected cells will fluoresce

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10
Q

What facilitates herpes mebrane fusion to host plasma membrane? What is the mechanism?

A

Viral fusion proteins. Receptor binding induces conformational changes in viral fusion proteins, pulling viral and host membranes together to induce fusion, pore formation and release of nucleocapsid into cytoplasm

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11
Q

How do herpesviruses get from the plasma membrane to the nucleus? Why must they use this method?

A

Via microtubules. Herpesviruses are to large to diffuse to nucleus and must use microtubules for transport.

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12
Q

What is the bulk flow direction along microtubules?

A

Retrograde: toward the nucleus

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13
Q

What happens to herpes tegument proteins upon virus entry?

A

They are released into the cytoplasm

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14
Q

What are the 2 main roles of tegument protieins

A
  • nucleocapsid trafficking

- undermining host defenses

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15
Q

Name 2 herpes tegument proteins and their functions

A

ICP0: E3 ubiquitin ligase that targets antiviral protein PML for the proteosome

VHS (virion host shutoff): enzyme that cuts host mRNA to prevent antiviral responses

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16
Q

What is the net effect of the tegument proteins?

A

Reduced production of antiviral interferon

17
Q

What is PML? What is its role?

A

Promyelocytic Leukemia protein: organizes spherical structures in the nucleus called PML bodies

18
Q

What are the functions of PML bodies?

A

Hubs for post-translational modifications with roles in anti-cancer and anti-viral responses
There is evidence that viral capsids can become trapped in PML bodies

19
Q

How do Herpesviruses get their genomes into the nucleus?

A

Their genome is inserted through nuclear pores

20
Q

What 3 things happen to herpes virus genomes when they enter the nucleus?

A
  • circularization
  • associate with histones
  • tether to host chromatin
21
Q

What are 2 advantages of latency for herpes virus infections?

A
  • carriage of vDNA through many cycles of cell division

- evasion of immune surveillance

22
Q

How does latency allow herpes viruses to evade immune responses?

A

Because few or no viral proteins are made and therefore there are no antigens available to present