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Virology30014 > L22: Enteric viruses - Norovirus > Flashcards

L22: Enteric viruses - Norovirus Flashcards

1
Q

Are most viral infections in the GIT acute or persistent?

A

Acute

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2
Q

What are the difficulties with GIT infections being acute? 1) 2) 3)

A

1) Hard to stop transmission as by the time you know you are sick the virus has probably spread to the next host
2) hard to diagnose as most people stay at home
3) difficult to control especially in large populations

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3
Q

What viruses penetrate the mucous layer in the Alimentary tract? 1) 2)

A

1) Adenovirus

2) Norwalk calicivirus

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4
Q

Describe how viruses obtain entry via the lymphoid follicles

A

M cells survey the lumen of the GIT and transcytose particles to underlying lymphoid tissues. Immune cells in peyers patches allow surveillance of GIT. Virus can pass through M cells to immune cells for spread

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5
Q

What is our primary defence against acute infections?

A

Innate immune response as acute infections are rapid

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6
Q

What is the importance of the adaptive immunity after acute infections?

A

essential for final clearance and memory

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7
Q

Describe characteristics of Norovirus 1) 2) 3)

A

1) ss+RNA
2) non-enveloped
3) encodes for a single capsid protein

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8
Q

What is the most common cause of viral GE?

A

Norovirus

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9
Q

How is norovirus ideal for infection 1) 2) 3) 4) 5)

A

1) Highly contagious
2) rapidly and prolifically shed
3) constantly evolving
4) evokes limited immunity
5) moderately virulent (infected fully recover)

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10
Q

What family is norovirus from?

A

Caliciviridae

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11
Q

List the clinical features of Norovirus infection

A

1) Faecal oral transmission
2) short duration
3) Nausea, fever, headache, abdominal cramping
4) watery diarrhoea and vomiting

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12
Q

What is the most prevalent norovirus strain?

A

Genotype GII.4

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13
Q

Why is genotype GII.4 so prevalent?

A

genotype GII.4 has many variants due to rapid evolution, antigenic variation and recombination

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14
Q

How does rapid evolution and antigenic variation occur in genotype GII.4

A

RdRp causes mutations in genome and then undergoes antigenic variation in response to herd immunity. Immunity also wanes as you get older

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15
Q

What are the 3 recombination hot spots in the ORFs

A

1) Overlap between ORF1 and ORF3
2) Overlap between ORF2 and ORF3
3) within ORF2

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16
Q

What does ORF2 encode?

A

The viral capsid

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17
Q

What does ORF1 encode?

A

replicative machinery

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18
Q

How does antigenic drift occur in norovirus?

A

Small mutations change surface of the virus, resulting in evasion of immune response

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19
Q

How does antigenic shift occur in norovirus?

A

Massive recombination, causing pandemic strains

20
Q

How does viral recombination occur?

A

Occurs with viruses of two different parent strains coinfect the same host and interact during replication to generate virus progeny that have genes from both parents.

21
Q

Does norovirus have a low or high ID

A

low infectious dose

22
Q

Can norovirus survive chlorination?

A

Yes

23
Q

What is the source of norovirus infections

A

Contaminated food/water

24
Q

Describe primary transmission for norovirus

A

contamination of food in the raw material stage or using contaminated food/sewerage on crops

25
Q

what is secondary norovirus transmission

A

Occurs during processing, storage and distribution and preparation

26
Q

How do you detect norovirus 1) 2) 3) 4)

A

1) Extract specimen from stool, vomit or environmental swabs
2) Immune EM (hallmark)
3) RT-PCR
4) Tissue culture systems

27
Q

What is the treatment and medication for norovirus?

A

1) hydration and electrolytes
2) avoid sugary drinks
3) IV fluids and electrolyte resuscitation if severe

28
Q

How long after infection can you still secrete norovirus?

A

4-6 weeks

29
Q

how long for norovirus symptoms to resolve?

A

1-2 days

30
Q

How to prevent norovirus infection

1) 2) 3) 4) 5)

A

1) Wash hands
2) sanitisation and disinfection of contaminated sites
3) monitor food handling
4) protect water supplies from contamination
5) education

31
Q

Why do we not understand much about norovirus replication and pathogenesis?

A

Because norovirus has limited cell culture under lab conditions, and there is no small animal model to study on

32
Q

Importance of STAT1 in mouse norovirus infection

A

STAT1 involved in IFN signalling (innate)

33
Q

Importance of RAG2 in mouse norovirus

A

RAG2 is involved in the adaptive immune response

34
Q

What happens when you knockout STAT1 in mouse norovirus infection

A

Mice with IFNa/B/yR (Type 1/2 receptors) or STAT1 knocked out succumbed to infection. This showed the innate response is essential for detection and clearance of MNV

35
Q

What is norovirus tropism?

A

1) Macrophages
2) Dendritic cells
3) Tuft cells

36
Q

Describe mouse norovirus genome

A

1) +RNA genome

2) small

37
Q

What does ORF1 encode for in mouse norovirus

A

1) NS6 - protease (cleaves polyprotein)
2) NS7 - RdRp
3) NS5 - VpG (binds to 5’ end to facilitate translation)

38
Q

What does ORF2 encode for in mouse norovirus

A

structural proteins - VP1 (capsid protein)

39
Q

What does ORF3 encode for in mouse norovirus

A

ORF3 encodes small basic protein VP2 produced from subgenomic RNA (minor capsid protein)

40
Q

what does ORF4 encode for in mouse norovirus

A

VF1 (virulence factor)

41
Q

What are key molecules that play an important role in controlling MNV-1 infection? 1) 2)

A

1) MDA5 - recognises RNA and triggers MAVS and makes IFN

2) STAT1 - controls infection through IFN signalling

42
Q

What are the 3 important discoveries from mouse norovirus

A

1) Role of microbiota (IFN-lambda) in persistent infection
2) Discovery of the MNV receptor
3) development of a cell culture system for Human norovirus

43
Q

How can we culture human norovirus

A

Human norovirus will grow in human intestinal organoids

44
Q

What is the MNV receptor discovered?

A

CD300lf

45
Q

What happens to a norovirus infection if you treat with IFN-lambda

A

You clear the infection.

Virology30014 (3 decks)

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