Lecture 7 Flashcards

1
Q

What evolutionary pressure is on viruses?

A

Development of strategies to escape the immune system for sufficient time to replicate and reinfect

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2
Q

What evolutionary pressure is on the immune system?

A

Development of multiple strategies to clear an infection but without causing unnecessary damage to host tissue

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3
Q

What four things can a cell do when it encounters a pathogen?

A

1) Clear the pathogen by phagocytosis 2) Present the antigen to the adaptive immune system 3) Alert and attract immune cells 4) Kill itself

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4
Q

Outline the basic activation of the innate immune system

A

1) Pathogen associated molecular pattern recognised 2) Signalling cascade to activate transcription factors 3) Transcription of anti-virulent factors, adaptive immune system recruitment molecules and apoptotic factors (also negative regulators of immunity to control the response)

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5
Q

Outline the downstream actions of IRF

A

IRF3 and 7 are activated by PRR and induce transcription of IFNß and IFNα (type 1 interferons). Type1 IFN’s cause transcription of interferon stimulated genes (ISGs) and bind the interferon A receptor which induces a second wave interferon stimulated genes via IRF and STAT

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6
Q

What are the functions of type 1 IFN’s in the immune system?

A
  • Inhibit protein translation in the cell - so virus cannt replicate
  • Induce cell death
  • Activate innate immune system (e.g. NK celss)
  • Activation of antigen presenting machinery
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7
Q

How can viruses escape IFN response?

A
  • Interfere with PRR sensing
  • Interfere with signalling downstream of PRR
  • Encode decoy IFN A receptor
  • Encode decory IRF receptor
  • Suppress activity of ISGs
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8
Q

How does influenza stop IFN activity?

A

NS1 protein binds to dsRNA and sequesters it from PRR

Also inhibits PKR - a kinase in the downstream from PRR

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9
Q

How does Karcosa-sarcoma herpes virus inhibit IFN immune response?

A

Inhibits IRF by having its own version of IRF which can outcompete cellular IRF

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10
Q

How Hepatitis C stop IFN immune activity?

A

NS3-NS4 protease is used to cleave signalling molecules, TRIF and MAVS,

NS5A inhibits PKR

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11
Q

What else if NS3-NS4 used for?

A

Cleaving protein products important for virus replication

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12
Q

How Hepatitis B stop IFN immune activity?

A

HBX causes degradation of MAVS

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13
Q

What other proteins will NS1 inhibit?

A

RIG-1, PKR and OASL

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14
Q

How can viruses escape apoptosis?

A
  • Inhibition of IFN response
  • Inhibition of TNF receptor
  • Inhibition of caspases
  • Inhibition of p53
  • Encode for pro-survival genes
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15
Q

What is a possible result of inhibition of p53?

Which virus’ are known for this?

A

Cancer

HPV - E6/E7 protein

KSHV - vGPCR

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16
Q

When was the first tumour inducing virus found?

What was it?

A

1964

EBV virus causes Burkitt’s lymphoma

17
Q

Which is the only transmissible cancer cell?

A

Canine transmissible venereal tumour

18
Q

How can viruses escape antigen presentation?

A
  • Down-regulate MHC class 1
  • Inhibit proteosome
  • Inhibit transport to cell membrane
19
Q

What antiviral activities do antibodies have?

A
  • Antibody-dependent cytotoxitcity
  • Complement activation
  • Antibodies for viral glycoprotein
20
Q

How can virus escape antibody acitivity?

A
  • Inhibitition of NK’s
  • Inhibition of complement
  • Mutation of envelope proteins
  • Directing antibodies to irrelevant epitopes on envelope
21
Q

Which receptor is supressed during KSHV?

Why is it surpressed?

A

TLR4

TLR4 mediates innate immune response against KSHV

22
Q

What disease can you develop if you have mutant TLR4?

A

Multicentric Castleman’s Disease

A lymphoma on top of KSHV

23
Q

How was TLR4 initially shown to be affected by KSHV?

A

TLR4 was the only toll-like receptor which had lower mRNA levels during KSHV infection

24
Q

What effect does UV treatment have on viruses?

A

DNA damage - so the virus can infect but can’t replicate

25
Q

What effect does heat inactivation have?

A

Destruction of envelope proteins, so the virus cannot infect cells