82 - Influenza Flashcards
Seasonal flu symptoms
Ranges from subclinical to severe Typical influenza involves fever/chills, cough, headache, muscle aches, fatigue, loss of appetite Chest X-ray normal Acute infection lasting about 7 days or longer; no persistence of virus; weakness and cough may last for several weeks
Percentage of population infected annually
10-20% of Australian population
Annual consultations due to flu in Australia
~1 million
Annual flu deaths in Australia
1,500
Annual global deaths due to flu
250,000 - 500,000
Influenza incubation period and infectious period
Incubation period 1 - 5 days; Infectious for 5 - 6 days
Flu receptor
Sialic acid-containing receptors in ciliated resp epithelium (AS alpha2-6 linkage to galactose in humans)
Where in the airways does flu particularly replicate?
Large airways (in epithelial cells of URT and LRT)
Cytokine leading to fever in flu
IL-1
Cytokine leading to malaise, headaches, muscle aches in flu
IFN
When does bacterial secondary infection become a danger with flu?
Late-stage infection can have replication in ciliated epithelium of trachea and bronchi gives bacteria a good place to replicate (H. influenzae, S aureus, S pneumoniae)
Can influenza cause pneumonia?
Can cause viral pneumonia only rarely. Mostly secondary bacterial pneumonia
Cause of flu death in elderly
From secondary bacterial infection
Family of influenza
Orthomyxoviridae
Flu virion structure
Enveloped, ssRNA (-)-sense, segmented genome,.
Types of influenza
A, B and C. No immunological cross-reactivity.
Influenza types that are major human pathogens
Type A and B. C is a minor human pathogen
*Influenza genome segment structure
Type of flu viruses that infect non-human species
Type A
Number of genome segments in flu
8
*Influenza virion structure
Anti-IFN flu protein
NS1
Number of RDRP subunits in flu
3
HA structure
Trimeric, elongated
NA structure
Tetrameric
Influenza type that is distinguished based on HA and NA types
Type A
Number of HA in type A
16
Number of NA in type A
9
Ancestral host of flu type A
Aquatic birds
At what pH does influenza escape endosome?
~pH=5
Current;y-circulating type A flu strains
H1N1 and H3N2
How does flu enter target cell?
RME
Tryptase Clara role
Cleaves HA in newly-budded virions to make them infectious. Reveals hydrophobic fusion protein.
Important cell in recovering from flu
CD8+ T cell
Types of flu antigens recognised by CTL
Internal antigens (which are conserved between type A subtypes, not between A and B).
How long-lived is CTL immunity against flu?
Not long-lived
Process responsible for ineffective anti-flu antibody response
Antigenic drift
Where do neutralising Ig against HA bind?
Overlapping epitopes in 5 sites around receptor-binding pocket
Where do mutations accumulate in flu HA?
5 sites around receptor-binging pocket
When does a flu strain arise against which there is no immunity?
When all five epitopes around binding pocket have mutated
Flu vaccine
Inactivated trivalent vaccine. Most recent strains of flu A H1N1, H3N2, and flu B (newer vaccines have 2 flu B strains)
People for whom a flu vaccine is recommended
People over 65 People with chronic lung, heart, kidney diseases With diabetes Immunosuppressed Health workers (might transmit to at-risk patients)
Where are flu vaccines grown?
In 10-day embryonated egg, in allantoic fluid.
Do flu vaccines induce CTL immunity?
No. Is an inactivated vaccine
Average flu vaccine efficacy
~70%
How long does it take to produce vaccine after strains have been predicted?
~6 months
Targets for flu antivirals
Ion channel blockers (M2) NA inhibitors
What does endosome acidification do to flu virion?
Reveals HA hydrophobic fusion protein. Allows endosome escape. M2 ion channel allows acidification of interior of virion, unlocks genome segments from capsid, allowing release of genome segments into cytoplasm.
Effect of amantadine, rimantadine
Block M2 ion channel. Inhibit uncoating of flu A virus in the endosome.
How are amantadine, rimantadine administered?
Orally, daily
How soon must zanamivir, ostelamivir be given?
Within two days of infection
Strains of flu showing resistance to zanamivir and ostelamivir
H1N1
How is Relenza administered?
Inhaled
How is Tamiflu administered?
Orally-administered prodrug
Human flu virus receptor
SA alpha2-6 linkage to galactose
Avian flu virus receptor
SA alpha2-3 linkage to galactose
Change required for HA specificity to either alpha2-6 or alpha2-3
Single amino acid change
Type of evolution of flu
Linear. Most-recent strain replaces previous strain
Possible pandemic flu configuration from antigenic shift
Human-adapted internal proteins, avian HA and NA (that aren’t recognised by human immune systems)
People particularly susceptible to swine flu
Pregnant women, obese people, indigenous populations
