Orthomyxoviruses Flashcards

1
Q

Which genome type?

A

(-)ssRNA with 8 segments

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2
Q

VRNP

A

Viral ribonucleoprotein structure - the 8 gene segments coated in NucleoProteins and polymerase proteins

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3
Q

What is the VAP?

A

Hemagglutinin

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4
Q

Neuraminidase

A

Envelope glycoprotein essential for replication.

Cleaves sialic acid to free hemagglutinin so it can bind an actual receptor not a dummy one in mucus as well as free budding viruses.

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5
Q

What category is this virus?

A

Enveloped and helical

(all helical animal viruses are enveloped)

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6
Q

What’s an example of an orthomyxovirus?

A

Influenza A-D

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7
Q

Influenza A

A

Seasonal, the only one to cause pandemics because of its large host range

Host range: birds, bats, humans, other mammals

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8
Q

Influenza B

A

Seasonal

Host range: humans, seals

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9
Q

Life cycle

A
  1. Attachment - VAP hemagglutanin & host sialic acid
  2. Penetration - endocytosis with acidification to cause endosomal membrane fusion
  3. Uncoating - full uncoating occurs in the nucleus
  4. Expression - vRNP goes to the nucleus and there’s primary transcription via virion associated polymerase. Splicing and translation occurs in the cytoplasm
  5. Replication - goes (-)ssRNA to (+)ssRNA back to (-)ssRNA. Includes secondary transcription and progeny nucleocapsid is transported out of the nucleus
  6. Assembly
  7. Maturation
  8. Release - budding
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10
Q

How can an 8 segment genome make 10 proteins?

A

(+)ssRNA splicing in the cytoplasm

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11
Q

What is the avian sialic acid receptor linkage?

A

alpha2,3

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12
Q

What is the human sialic acid receptor linkage?

A

Alpha2,6

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13
Q

Why is sialic acid receptor linkage important?

A

Determines host range which is a big barrier to spillover

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14
Q

How are (-)ssRNA genes expressed?

A

Packaged RNA dependent RNAP converts (-)ssRNA to (+)ssRNA which = mRNA

Host translates (+)ssRNA

New (+)ssRNA converted to (-)ssRNA to replicate the genome

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15
Q

How does IAV know what is vRNP, vRNA, or mRNA?

A

vRNA - uncapped (-) sense
mRNA - 5’ cap stolen from host and (+) sense
vRNP - is the prepackaged structure of genome segment and (-) sense

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16
Q

Cap snatching

A

IVA polymerase is a cap-dependent RNA endonuclease

Steals 5’ host mRNA cap for its own mRNA

Viral mRNA are hidden and host mRNA aren’t made

17
Q

Which animal is the influenza mixing vessel and why?

A

Pigs because they can get avian, swine, and human influenza and spread each or have superinfection and reassortment

18
Q

The 5’ host mRNA cap does what?

A

Acts as a primer and hides the viral mRNA from the immune system

19
Q

What causes influenza’s seasonality?

A

Main - higher humidity = lower transmission

Water droplets in air weigh viral particles down so they can’t spread as far

20
Q

Where is the reservoir if it’s seasonal?

A

It’s always around evolving but is year-round in the tropics (mostly SE Asia)

21
Q

Antigenic drift

A

Gradual accumulation of minor mutations in the viral genome which can subtly alter antigenicity

Decreases immune recognition
Leads to seasonality
More frequent in RNA viruses because RNAP is more error prone

22
Q

Antigenic shift

A

A sudden and dramatic change in the antigenicity of a viruses due to reassortment of a segmented genome with another of a different antigenic type

Virus suddenly unrecognizable
Has lead to several influenza pandemics

23
Q

Influenza symptoms

A

Common - fever, cough, congestion, viral pneumonia, myalgia

Rare - Reye’s syndrome (swelling of liver and brain), influenza encephalitis

24
Q

Influenza transmission

A

Respiratory droplets
Fomites- contaminated object

25
Q

Risk factors

A

Age - extremes
Immunosuppression
Pre-existing conditions

26
Q

Antiviral drugs

A

Neuraminidase inhibitors - inhibits release, late stage drug

Endonuclease inhibitors - inhibits 5’ cap stealing to inhibit replication, preventative or early stage drug

27
Q

Vaccination strategies

A

Inactivated - egg or tissue-culture based propagation (intramuscular)

Live attenuated - influenza strain used is temperature sensitive and grows poorly at 37C (intranasal)

28
Q

Antibodies attack what?

A

HA and NA antigens

29
Q

How could they make a universal flue vaccine?

A

Target antigenic-ally conserved stalk region of HA

30
Q

How do you get new human influenza pandemic strains?

A

Reassortment with avian genome segments

31
Q

Why did the 1918 pandemic cause so much death in 15-45 year olds?

A

Imprinting or “original antigenic sin” - the first H strain you are exposed to is the dominant response you’ll ever produce

Older generation had previously been exposed to another H1 viruses

Middle generation were exposed to a H3N8 virus and had no preexisting immunity to H1 viruses like the 1918 one

32
Q

H7N9

A

Could be next pandemic

40% mortality
Commonly produces pneumonia
Human to human spread

33
Q

H5N1

A

Could be next pandemic

50% mortality
Dramatic spread in birds
Limited human to human spread