Influenza Flashcards
What are synonyms of influenza?
Flu, grippe
How is influenza spread?
By aerosols very efficiently
What is influenza?
An acute viral infection involving the respiratory tract
What is the incubation period of influenza?
1-3 days
How long does influenza last?
3-10 days
What does infection lead to?
Cell killing and local inflammatory responses
What happens after cell killing?
Chemokines and cytokines (macrophages) that cause the symptoms: fever, muscle ache, headache, prostration, anorexia. ‘Cytokine storm’
Is death from primary infection of influenza common?
Death from primary infection is rare.
Is death from secondary infection of influenza common?
Cell damage predisposes to secondary bacterial infections with deaths, especially in the elderly
What was the mortality rate of the Spanish flu?
Mortality rate was 2.5% compared to previous epidemics of 0.1% i.e. more than 20x higher
How many deaths were there due to the Spanish flu?
> 40 million deaths (could have been up to 100 million?)
What was the 1918 pandemic virus caused from?
Virus genome sequenced from permafrost burials
Whats the originator of HA virus?
Birds
When were the genetic elements of the 1918 virus estimated to be circulating from?
1911
What is done to understand the pathology of pandemoc viruses?
Partial reconstruction used in animal experiments
What are the 3 distinct serotypes?
A type
B type
C type
What is the A type serotype?
Viruses infect mammals, including humans, horses, pigs, ferrets and birds. Cause epidemics and pandemics
What is the B and C type serotype?
B- and C-type viruses infect only humans & are not as severe as A types
(some evidence of B in horses, and C in dogs and pigs)
What are the important reservoirs in generating new viruses?
Pigs and birds
What is the structure of the virion?
Lipid envelope with 2 projecting glycoproteins
Envelope inner side is lined by matrix protein (M1)
Inside are 8 ribonucleoprotein (RNPs) genome segments
Lacks RNA proof-reading enzymes
Not a retrovirus- no DNA step, no genome integration
What are the 2 glycoproteins in the lipid envelope?
Haemagglutinin (HA), a trimer
Neuraminidase (NA), a tetramer
What are the 3 important genome segments- RNA encoding?
Haemaglutinin- major antigenic glycoprotein
Neuraminidase- virus release
Matrix- major virion component
What are the serotypes of influenza virus?
15 HA and 9NA
What is the nomenclature of influenza virus strains?
A (type) Singapore (town) 6 (first isolated number of isolates) 86 (year of isolation) (H1N1) type of HA and NA
What happens when a strain goes under minor changes?
Absence of RNA proofreading enzymes, the RNA-dependent RNA polymerase that copies the viral genome makes an error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA
What happens when a strain goes under major changes?
Every 10-15 years worldwide a new pandemic strain appears in humans with a totally new HA and sometimes a new NA (‘antigenic shift’)
What do changes to strains do?
Enhance the virus’s ability to infect host & evade the immune system
What do separate genome segments facilitate?
Genetic exchange between different strains. Reassortment (very rarely recombination)
What does exchange of genes cause?
New combinations of HA and NA to be expressed on the viral envelope
What are antigenic ‘drift’ minor changes?
Minor mutations in one or more of 4 HA regions
Genome is (-) RNA so mutation/error rate is high
Single amino acid substitiutions accumulate that evade antibody specific to previous strains/infections
Effects are evident over 2-3 years
Occurs in all A,B and C strains
What is 1 of the major changes of antigenic shift?
A new HA is acquired (plus sometime new NA) that is crucial for infection & cell entry
Exclusive to A strains
Enables influenza virus to cause pandemics
What is the 2nd of the major changes of antigenic shift?
Uses ‘mixing vessels’ e.g. pigs that are susceptible to both bird & human strains
Complete genome segments can be exchanged between these viruses if they infect the same cell
•New recombinant virus
What does H5N1 cause?
Lethal bird flu, deciminating flocks of domestic poultry
How many people were infected with H5N1 in 2015 and how many deaths were there?
638 infected
379 deaths
Why does the H5N1 virus fizzle out?
Virus is not (yet) adapted to humans
What position is H5 HA and what does this mean?
Has glutamine at position 226- i.e. is avian and poorly adapted to humans. But, with a single mutation to HA226 leucine (as in human viruses) big trouble
What are other strains of avian influenza viruses?
Many subtypes, 4 of which are highly pathogenic humans- H5N1, H7N3, H7N7, H7N9 and H9N2
What is the treatment with M2 inhibitors?
Amantidine and rimantadine drugs are active against most A strains
Bind M2 protein
Drug- treated cells cannot lower the pH of endosomes causing uncoating, an M2 function
What does treatment for M2 inhibitors work for?
A-type viruses
What is treatment of neuraminidase inhibitors?
11 universally conserved amino acids form the NA active site. Synthetic sialic acid analogues are NA enzyme inhibitors
What does neuraminidase inhibitor treatment work for?
Against all A and B strains
What types of viruses are required?
HA type
What is required for a virus?
Large amounts are grown in embryonated eggs (cheap and efficient) purified and formalin inactivated
How much protection does the influenza virus vaccine give?
60-80%
What do the WHO have to do every year in regards to creating a vaccine?
A decision must be made in August as to which HA type to use the following winter. A monitoring system worldwide helps make this decision
WHO recommends strains that should be targeted in the following winter’s vaccines.
How many combinations of genes for influenza are possible?
256 combinations
Who is the flu vaccine normally given to?
Live attenuated (temperature- sensitive) flu immunisation, up nose, for children up to 5 or 6
