Lecture 12-Influenza Flashcards
why is influenza important
ubiqitous in human populations-influenze A is a zoonosis
very common cause of illness
common cause of death-elderly
epidemics
large social/financial impact
model for recurrent infection despite development of immunity
influenza viral particle
orthomyxoviridae
envelope derived from host cell-bud off don’t explode host cells
envelope glycoproteins of critical importance in virus entry and egress from cells
single stranded RNA negative sense virus- segmented which makes it easy to share RNA
2 most important viral proteins within the viral envelope
neurominidase and hemaglutinin
Influenza A
a bird virus
humans are incidental hosts
lots of subtypes
-defined by surface glycoproteins: neuraminidase (cleaves H from salialic acid as virus leaves host cell. and hemaglutinin (viral attachment to cell membrane salialic acid in resp cells allowing entry into cell).
-strains named by H and N type and place/year of origin
can be non pathogenic (cause no illness) or lowly
-H1N1 means first type of haemaglutininin and first type of neurominidase. A/H1N1/Mexico city 2009
pathogenic (some affected birds that get mild gastro intestinal illness as influenza A affects birds GI tracts) or highly pathogenic (it’s capacity to kill birds not humans).
Influenza B
a human virus
causes epidemics but not pandemics because theres no possibility of new types of virus
no subtypes
-only one type of hemaglutinin and neuraminidase- do change and evolve though
-strains named after year and place of origin. e.g.. influenza B/Shanghai/2005
Seasonal infleunza
only 3 strains that populate humans
-AH1N1 (“spanish flu” in 1918 didn’t affect older people but has stayed in populations), AH3N2 and B
-in temporate zones, flu season is in winter
-in tropics it is all year round
infection in most people is severe but not life threatening
no flu circulating during summer months.
If recovery from influenza infection results in immunity- how do we get further infections and epidemics each year?
They are immune to that particular strain for that winter but they may get infected with A/H1N1 in 2020 or 2022. This is because RNA virus has no proof reading capacity so when it replicates its RNA or its genomes it makes mistakes. many mistakes are terminal and don’t work because they don’t encode for anything but sometimes its a mutation that changes the amino acid structure of the protein therefore reaching a point where our antibodies are no longer able to neutralise hemaglutinin, no longer able to stop hemaglutinin binding to resp. cells and this is when we can get sick again. known as antigenic drift.
antigenic drift
primarily due to haemaglutinin. the virus is slowly changing over time that once the mutation is great enough the antibody will no longer recognise it and you are now susceptible. A and B are always undergoing this. children are susceptible every 3 to 4 years. adults its 6-8 years.
Haemaglutinin function and antigenic drift
viral attachment to cell membrane salialic acid in resp cells in back of nose and throat allowing entry into cell. past infection with a similar strain of virus- IgA antibody to haemaglutinin and infection will be prevented. As H1 changes the antibody to H1 will completely prevent H1 binding to sialic acid and may partially prevent binding of the changed H1’s. this results in partial immunity to closely related strains of influenza- maybe minor illness or no symptoms at all. Minor alterations in the hemaglutinin may prevent antibody attachment- ‘new’ strain can cause infection.
neurominidase function
main drug for influenza is a neuraminidase inhibitor. As the flu in budding off the cell its stuck to host cell due to hemaglutinin. neuraminidase cleaves the sialic acid receptor to allow the virus particle to bud off. with drug the viral particles remain stuck and can’t go off and invade other cells.
if these inhibitors aren’t administered early on it is useless which is its main fault.
How does influenza cause disease?
The infection of epithelial cells and budding off is so great that the cells are damaged and destroyed in time (partly cytopathic). viral production is very quick, peaks at 2 days. incubation period is very short and viral replication coincides with symptoms, people feel at their worst at the beginning. They feel bad due to immune reponse, especially interferon alpha (peaks when symptoms feel worse)
Why do you die of Influenza?
The cytokines get out of control and they’re in multi organ failure.
The damage to the lung is so great that oxygen can’t be transferred.
Transmission of the flu
droplet spread- infected ferrets unable to infect non infected ferrets when caged together but separated by a low barrier. involves contact of the conductive or mucus membranes of the nose or mouth with large particle droplets
- large droplets are generated during coughing or sneezing or talking
- requires close contact less than a metre
contact spread- virus can remain viable on a smooth surface for 24 hours. generally not infectious once secretions have dried
Oseltamivir and its uses
neuraminidase inhibitor. reduction of duration of illness by about half a day if you get onto it very early. good if you get it in the first 6 hours of flu. main role could be in prevention, if someone gets the flu in a rest home you could find out who they’d be in contact with and before those people got sick give them the drug to prevent illness. 70-90% reduction.
current flu vaccines-trivalent and problems
each vaccine contains antigen from AH1N1, AH3N2 and B
contains the circulating strain that scientists think will be the strain to affect humans this winter and a laboratory strain which has been changed so it doesn’t have the capacity to cause disease. they will recombine these so the neuraminidase gene and hemaglutinin gene are now in the safe virus, non pathogenic virus. virus is then cultivated in chicken embryos, inactivated, broken into pieces and importantly the virus is split and then washed so you don’t ever end up with virus RNA in the vaccine. what you have is the hemaglutinin antigen
problems:
seed virus takes a long time to re-assort, may not match circulating strain closely.
seed virus needs to be passaged many times to increase yeild
efficacy related to ability to produce circulating IgG to H antigen
