Influenza Flashcards
What is the incubation period of influenza?
1-5 days
What is the infectious period of influenza?
5-6 days
What receptors do the influenza virus bind to?
Sialic acid containing receptors on non-ciliated respiratory epithelium
What type of linkage does sialic acid have to galactose in humans?
alpha2-6 linkage
Where does the influenza virus replicate?
in epithelial cells of upper and lower airways - particularly in the bronchi
Which cytokine produced by the inflammatory response to influenza virus results in fever?
IL-1
Which cytokine produced by the inflammatory response to influenza virus results in muscle aches?
IFN
Where might replication occur later on in the influenza infection?
In ciliated epithelium of trachea and bronchi
What pathogens may cause a secondary bacterial infection after an infection of influenza?
H. influenzae, staph aureus, strep pneumoniae
Which family is the influenza virus a member of?
The orthomyxoviridae family
What feature is unique to influenza and rotavirus?
Segmented genome
How many segments are there in influenza?
8
What type of genome is influenza?
- sense ssRNA
What types of influenza are there based on their immunological cross reactivity?
Type A, B and C
Which types are human pathogens?
A and B
Which type can infect other species?
Type A
What are the features of the virion?
Envelope, glycoproteins on the surface (haemoglutinin and neuraminidase), matrix, 8 ribonucleoproteins, M2 protein (ion channel), NEP protein (for replication)
What non structural protein is there in influenza?
NS1 - to counteract interferons
How many genes does influenza encode?
10+
What is the action of haemoglutinin?
Binds to sialic acid to initiate entry
What is the action of neuraminidase?
Binds to sialic acid and cleaves it off to prevent other influenza viruses binding - this prevents influenza from re-infecting the same cell after it leaves
What is the structure of haemoglutinin?
trimer with 3 receptor binding pockets
What is the structure of neuraminidase?
tetramer
What differs between the different subtypes of type A influenza?
The structure of HA and NA
How many different types of HA are there?
17
How many different types of NA are there?
10
What two subtypes of type A are currently in human populations?
H1N1 and H3N2
What allows the influenza virus to leave the endosome after endocytosis?
A natural drop in pH as the endosome moves closer to the nucleus results in a change in HA which allows the viral envelope to fuse with the endosome and form a pore
How does the influenza virus leave the infected cell?
HA and NA are glycosylated in the ER and golgi and then expressed on the cell surface and the RNPs bud out from beneath
What confines influenza to the respiratory tract even though the receptor that it binds to is located throughout the body?
Influenza virus requires the enzyme tryptase Clara which is only in the respiratory tract
What is the action of tryptase Clara in making influenza infectious?
It cleaves HA to reveal a hydrophobic fusion peptide - this allows HA to fuse with the endosome so that the virus can enter the cytoplasm
What are the adaptive immune responses to influenza?
CD8 T cells kill virus infected cells - this keeps viral loads down until specific antibodies develop
What antigens do CD8 T cells recognise?
internal peptides that are highly conserved unlike HA and NA
What antigen to the antibodies bind to?
5 sites surrounding the receptor binding pocket of HA - neutralises the pathogen by preventing it from binding to its receptor
Why are we continually infected with influenza despite developing antibodies?
Because antigenic drift creates new antigenically distinct strains of virus
Why does antigenic drift occur in influenza?
Because RNA dependent RNA polymerase makes a lot of errors
Why is there only ever one strain of a subtype in the the population?
Because there is linear progression of antigenic change and new strains replace older strains
What does the influenza virus contain?
The most recent strains of H1N1, H3N2 and type B that have been inactivated so won’t induce cytotoxic T cells but will produce antibodies
What is the action of relenza and tamiflu?
Inhibits NA so that the virus will keep reinfecting the same cell - blocks efficient release
What is the action of amantidine and rimantidine?
Blocks the M2 ion channel which acidifies the inside of the virus to allow the conformational change in HA to get the envelope to bind to the endosome and the virus to be released
What type of influenza are ion channel blockers not active against?
type B
What is the disadvantage of ion channel blocker anti virals?
They genera drug resistant mutants
How are amantidine and rimantidine administered?
orally, daily
How are relenza and tamiflu administered?
relenza is inhaled, tamiflu is given orally - both are given twice daily within two days of developing symptoms
What is antigenic shift?
The sudden appearance of a new type A within the human population from zooinosis - results in a pandemic
Why are pandemics rare?
Because birds (which influenza usually infects) have alpha2-3 linkage of sialic acid instead of the human alpha2-6 linkage - so a mutation would require an amino acid change which allows HA to now bind to the alpha2-6 linkage
Why are pigs a mixing vessel for reassortment of influenza?
Because they have both alpha 2-6 and alpha 2-3 linkage
What has antigenic shift resulted from?
direct infection with avian virus in 1918, genetic reassortment in 1957 and 1968 and reintroduction of previous human strains in 1977
What was special about swine flu?
The virus had a greater ability to replicate in lungs
What is special about the current avian H5N1?
It doesnt require tryptase Clara so is systemic - so it is lethal in humans - however it hasn’t yet infected man to man
