Influenza Flashcards
Clinical -Influenza
-virus replicates in epithelial cells of respiratory tract
Clinical -Pathogenesis
- Spread by aerosols is very efficient
- incubation period 1-3days , disease lasts 3-10 days
- Infection–> cell killing &local inflammatory responses –> release chemokines and cytokines that cause symptoms: fever, aching, etc
Spanish flu 1918-19
pandemic
- mortality rate was 2.5%
- > 40 million deaths
- origin=birds
Molecular biology:
A-type infect mammals and birds
B- and C- types infect humans
Structure of virion:
Lipid envelope with 2 projecting glycoproteins:
- haemagglutinin (HA) trimer
- neuraminidase (NA) a tetramer
- envelope lined (inner) by matrix protein (M1)
- Inside are 8 ribonucleoprotein RNPs genome segments
-not a retrovirus
8 RNPs each contain:
- (-) sense ssRNA
-3 polymerase subunits
-NP
8 segments code for 16 proteins
Neuraminidase required
for release of virion
Epidemiology
Minor changes -antigenic drift
-mutations in one or more of 4 HA regions
Major changes -antigenic shift
-a new HA is acquired that is crucial for infection and cell entry
-exclusive to A strains
-enables influenza virus to cause pandemics
Distribution of Sialic/Neuraminic acid
- in bronchioles and alveoli in lungs
- in entire GI tract in chicken/bird
‘Bird’ flu - H5N1
-spreads slowly, often fatal
treatment - 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
- only works for A-type viruses
Treatment (II)
neuraminidase inhibitors
- tamiflu and relenza
(i) attachment
(ii) endocytosis
(iii) replication
(iv) budding
(v) no virion release
Vaccines
-live attenuated (temp sensitive) ‘flu immunisation, up nose, for children up to 5 or 6’
Haemagglutinin (HA)
binds mucoproteins on epithelial cells
containing terminal sialic acid groups
