Influenza Flashcards
What is the function (generally) of HA, NA and M2
HA:
Attachment and penetration through recognition of sialic acid receptors.
NA: cleaves sialic acid from glycoconjugates to facilitate elution of progeny virions from infected cells.
M2: Uncoating and virus maturation… After infection of cell, viral RNA needs to be released into host cell..
What is influenza?
An Orthomyxovirus that contains ssRNA, and is enveloped.
Infleunza contains 3 antigenic targets - Hemmaglutinnin HA, Neuraminidase NA, vRNA.
aswell as the M2 ion channel.
Influenza recognises sialic acid receptors.
What is the structure of HA?
2 domains - globular head and fibrous stem.
Globular head recognises and binds receptor sialic acid.
Binding sialic acid, causes conf. change to bring virus close to cell surface.
What is sialic acid?
Sialic acid is often the terminal carbohydrate on cell surface glycoproteins.
What is the structure and function of NA?
NA hydrolyses sialic acid from its respective surface glycoprotein.
Once removed, HA no longer binds = essential for efficent elusion of viral progeny after infection.
What is the initial response to influenza infection?
A typical innate and pro-inflammatory response.
NFkB transcription leads to release of pro-inflammatory cytokines like TNFa, IFNb and IL-8.
Chemokines attract NK, B and T cells to site of infection.
= Which respond by producing more - TNFa, IFNy, IFNa/b, and IL-1b…
- to keep Th1 response cycle going.
What is the long term esponse?
IFN-y release by NK, B, T cells increases chemokine gene expression and activates macrophages.
Antigenic presentation and cell-mediated immunity are boosted by IFN-y.
There is a Th2 response, antigenic presentation and B cell activtion and maturation.
= Leading to antigen-specific IgG antibody production.
Particularly IgG1 antibodies and generate memory B cells to protect against similar re-infection.
IgG antibodies produced only recognise the one subtype of H or N it was generated against…..
What are the types of influenza?
4 types: A, B, C, D.
A and B cause human influenza seasonal epidemics every winter.
Type C causes mild respiratory ilnnes, and Type D infects cattle and aren’t known to infect humans.
What are the sub-types of influenza A?
Influenza A viruses subdivide into subtypes based on HA and NA.
18 subtypes of HA and 11 of NA.
HA1-18 and NA1-11.
Current influenza A subtypes:
H1N1 and H3N2.
IgG antibodies produced only recognise the one subtype of H or N it was generated against…..
What is antigenic drift?
Gradual accumulation of AA mutations in HA r NA, allow escape neutralising antibodies.
Epidemic strains tend to have 3 or more changes to antigenic sites.
= Reduced ability of circulating IgG antibodies (IgG1) to recognise “new” viral antigens.
= resulting in seasonal influenza.
What is seasonal influenza?
Most common form of Influenza A virus that tends to comprise a variant of a previous strain.
Since derived from previous strain, much of populiation already has partial immune protection BUT
As a result of antigenic drift of previous strain, with reduced ability of circulating IgG antibodies to recognise “new” viral strain antigens.
Seasonal influenza often bigins increasing in october, with peak between December adn February….
Development of vaccine to seasonal flu?
Begin innoculations of vulnerable individuals around october, such that enough time for individual to mount an effective immune response, form memory B cells and IgG antibodies before flu activity peaks in December to february…
What is pandemic/epidemic influenza?
A new strain which can possible be of non-human origin (often pig or bird)..
What is antigenic shift?
Genetic reassortment - entire genes encoding different HA or NA subtypes are incorporated into the “new” virus.
An instantaneous, complete change to viral genome during a single replication cycle.
Often occurs in animal hosts that are co-infected with 2 different strains of influenza.
Since derived usually from animals, HA and NA subtypes will be different to usual encounter - population will lack any partial immunity from previous exposure to similar strains.
= NO immune history.
Highly pathogenic with high mortality and is completely unpredictable.
Disease severity/mortality can lack distinction between at risk and healthy adults..
H1N1 Swine Flu.
What are drug names for influenza?
Adamantanes (M2 inhibitors).
Amantadine and Rimantadine
BUT NEITHER ARE NICE RECOMMENDED.
NA inhibitors:
Olseltamivir = Tamiflu.
Relenza - Zanamivir
