Influenza Virus Flashcards
Where does influenza virus replicate?
Ø Replicates in upper respiratory tract in humans
Ø Replicates in the intestines and respiratory tract in birds
Give some of the properties of the influenza virus
Member of the orthomyxoviridae family
Enveloped virus (80-120nm)
Negative-sense, ss, RNA genome
Why is antigenic shift important for the influenza virus?
- Complete change in subtype of HA or NA
- Change in HA can result in pandemics
- Reassortment causes a shift in species
Describe the life cycle of the influenza virus
- Attachment: HA binds to sialic acid
- Entry: Receptor-mediated endocytes
- Virus replication: occurs in the nucleus
- viral mRNA need to be capped at their 5’ end (5’C)
- some viral mRNAs are spliced
Capping tand splicing enzymes are in the nucleus - Exit: by budding, Neuraminidase aids release of the virus from the cell
Why is antigenic drift important for the influenza virus?
- Variation within the HA or NA subtype
- Drift in HA or NA results in epidemics and more rarely pandemics
- Can also allow influenza to jump species
- Can cause changes in the virulence/tissue tropism
What is antigenic shift/reassortment? in the case of influenza.
Complete change in HA type
Virus acquires a different HA type from a different species as a result of re-assortment of the viral segments
Pigs generally act as mixing vessels as they can be infected with both human and avian viruses
Causes pandemics
Population are immunilogically naive
host immune system has not seen this gene before
No protection
What does antigenic drift causes variation in spike proteins present of the viral surface?
Ø Produce viruses with slightly different amino acids composition
Ø Some may grow better on particular host than others
Ø Gradual accumulation of antigenic mutations
Amino acid changes caused by antigenic drift lead to…?
Change in host (species specificity)
Change in tropism
What does Haemagglutinin protein do why is it important in receptor binding site and cleavage site?
Most abundant protein on the viral surface and is the main target of immune response
Receptor site:
- Allows virus to bind to sialic acid on host cells
- Enables virus internalisation (within endosome)
Cleavage site:
- Cellular proteases cleave HA into the 2 subunits to allow virus release from the endosome
- Cleavage aids fusion of the virus membrane with membrane of the vesicles
- How well HA is cleaved by cellular proteases facilitates virus entry
Which H types cause all pathogenic forms of the avian influenza?
H5 and H7
Whats the difference between a low pathogenic and high pathogenic avian influenza?
Low pathogenic avian influenza:
Ø HA1 & HA2 polypeptide chains linked by single arginine residue
Ø Cleaved by a few cellular proteases found in a limited subset of cells
Ø Therefore influenza normally can only replicate in a few cell types
High pathogenic avian influenza:
Ø Insertional mutations add basic residues at HA cleavage site
Ø HA1 & HA2 polypeptide chains linked by several basic AA residue
Ø Cleaved by ubiquitously expressed cellular proteases (furin and other subtilin family proteases
- Virus can replicate throughout birds body producing necrotic foci in many places
How can changes in receptor binding can cause change in species specificity?
Sia-alpha2,6Gal: Present in the human upper resp tract therefore human viruses can enter and cause infection
Sia-alpha2, 3Gal: Present in the human lower resp tract therefore avian viruses can enter and cause infection but only when in close contact with avian viruses
So therefore under normal circumstances the avian virus is restriced to birds
Whats the difference between H1N1 and H5N1?
H1N1 spreads easily but is rarely fatal
H5N1 spreads slowly but is often fatal
What changes in the HA of H5N1 can cause a change in species specificity?
Several mutations have been implicated
- Reduce binding to Sia-a2-3Gal
- Increase binding to Sia-a2-6Gal
For H1/H3 as few as 2 AA can switch human and avian receptor specificity
Whats the adaptation of influenza H5 to replicate and transmit efficiently in ferrets?
Ø Required just 4 mutations in HA
- Three for binding to Sia-Alpha 2-6Gal (Human HA receptor)
- One for stabilising the HA
Whats the immune response against Haemagglutinin?
Neutralising Ab target the globular head of HA
- Neutralise virus by binding to or near the receptor for host cells
- Therefore blocks binding and entry ofvirus to cell
Are strain-specific and lacks cross neutralising Ab to different HA subtypes
Are epitopes on the stalk/stem region
- Conserved amongst the differnt HA subtypes
- Can be broadly neutralising against many HA subtypes but titres are low during infection
What is the immune response to Neuraminidase
NA plays an important role in allowing release of influenza from the cell
After bunning NA cleaves sialic acid from receptors–> destroys the receptor and prevents reinfection of the same cell
Ab to NA can block this enzymatic activity
-Therefore, do not prevent infection but limit virus spread
-But do reduce replication by inhibiting the release of newly produced viral particles (reduce severity adn length of infection)
What is the cellular immune response to influenza?
CD4+ and 8+ T-cells are induced by:
- Envelope proteins (HA & NA)
- Internal proteins
CD8+ T cells
- Eliminate virus infected cells :
- release perforin and granzyme
Release IFN gamma and TNF alpha
Epitopes are conserved within subtypes so may be cross-protective
