Orthomyxoviruses Flashcards
Which genome type?
(-)ssRNA with 8 segments
VRNP
Viral ribonucleoprotein structure - the 8 gene segments coated in NucleoProteins and polymerase proteins
What is the VAP?
Hemagglutinin
Neuraminidase
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.
What category is this virus?
Enveloped and helical
(all helical animal viruses are enveloped)
What’s an example of an orthomyxovirus?
Influenza A-D
Influenza A
Seasonal, the only one to cause pandemics because of its large host range
Host range: birds, bats, humans, other mammals
Influenza B
Seasonal
Host range: humans, seals
Life cycle
- Attachment - VAP hemagglutanin & host sialic acid
- Penetration - endocytosis with acidification to cause endosomal membrane fusion
- Uncoating - full uncoating occurs in the nucleus
- Expression - vRNP goes to the nucleus and there’s primary transcription via virion associated polymerase. Splicing and translation occurs in the cytoplasm
- Replication - goes (-)ssRNA to (+)ssRNA back to (-)ssRNA. Includes secondary transcription and progeny nucleocapsid is transported out of the nucleus
- Assembly
- Maturation
- Release - budding
How can an 8 segment genome make 10 proteins?
(+)ssRNA splicing in the cytoplasm
What is the avian sialic acid receptor linkage?
alpha2,3
What is the human sialic acid receptor linkage?
Alpha2,6
Why is sialic acid receptor linkage important?
Determines host range which is a big barrier to spillover
How are (-)ssRNA genes expressed?
Packaged RNA dependent RNAP converts (-)ssRNA to (+)ssRNA which = mRNA
Host translates (+)ssRNA
New (+)ssRNA converted to (-)ssRNA to replicate the genome
How does IAV know what is vRNP, vRNA, or mRNA?
vRNA - uncapped (-) sense
mRNA - 5’ cap stolen from host and (+) sense
vRNP - is the prepackaged structure of genome segment and (-) sense
Cap snatching
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
Which animal is the influenza mixing vessel and why?
Pigs because they can get avian, swine, and human influenza and spread each or have superinfection and reassortment
The 5’ host mRNA cap does what?
Acts as a primer and hides the viral mRNA from the immune system
What causes influenza’s seasonality?
Main - higher humidity = lower transmission
Water droplets in air weigh viral particles down so they can’t spread as far
Where is the reservoir if it’s seasonal?
It’s always around evolving but is year-round in the tropics (mostly SE Asia)
Antigenic drift
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
Antigenic shift
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
Influenza symptoms
Common - fever, cough, congestion, viral pneumonia, myalgia
Rare - Reye’s syndrome (swelling of liver and brain), influenza encephalitis
Influenza transmission
Respiratory droplets
Fomites- contaminated object
Risk factors
Age - extremes
Immunosuppression
Pre-existing conditions
Antiviral drugs
Neuraminidase inhibitors - inhibits release, late stage drug
Endonuclease inhibitors - inhibits 5’ cap stealing to inhibit replication, preventative or early stage drug
Vaccination strategies
Inactivated - egg or tissue-culture based propagation (intramuscular)
Live attenuated - influenza strain used is temperature sensitive and grows poorly at 37C (intranasal)
Antibodies attack what?
HA and NA antigens
How could they make a universal flue vaccine?
Target antigenic-ally conserved stalk region of HA
How do you get new human influenza pandemic strains?
Reassortment with avian genome segments
Why did the 1918 pandemic cause so much death in 15-45 year olds?
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
H7N9
Could be next pandemic
40% mortality
Commonly produces pneumonia
Human to human spread
H5N1
Could be next pandemic
50% mortality
Dramatic spread in birds
Limited human to human spread
