Influenza (3)-Leah Flashcards
Influenza
- Virus family:
- genome type:
- shape
- orthomyxovirus
- negative SS RNA (8 segments)
- enveloped helical nucelocapsid
Important proteins on influenza viral membrane (3)
hemagglutinin (HA; Neuramidase (NA); M2
Components of influenza nucelocore (3)
- the 8 RNA segments
- nuclear matrix protein (M1)
- nucleoprotein (NP)
How many types of influenza are there?
Which are clinically relevant?
A,B,C
*C does not cause human illness
How are influenza viruses grouped into classes?
Subtypes?
Classes based on nucleocore proteins (M1, NP)
Subtypes based on membrane proteins (HA, NA)
Two recent major flu strains:
H1N1; H2N3
Remember: 1,1,2,3
In both epidemics and pandemics, what proteins are altered?
HA, NA- membrane proteins
subtypes change; classes do not– always A,B,C
How does antigenic drift occur?
How does shift occur?
What is the result of each?
drift: gradual change via point mutations= epidemic
shift: sudden change via reassortment= pandemic
Which influenza virus classes undergo shift/ drift?
shift: seen in both A and B
drift: has only been seen in influenza A
When and why does flu peak?
Dec- March
*low temp and humidity
How is flu transmissed?
- respiratory droplets
- contaminated surfaces
What are the very basic functions of hemagglutinin and neuramidase?
HA- mediates viral ENTRY by binding sialic acids
NA- mediates RELEASE of virus progeny after replication
What determines the anatomical location of influenza infection?
HA type! – HA mediates entry
*Multiple sialic acid receptors exist in body; HA type determines what cells the virus can enter (& therefore location of infection)
Human influenza virus has a hemagglutinin capable of binding what sialic acid type? What is the implication?
-binds a2,6 sialic acid =
infection of tracheobronchial epi/ type 1 pneumos
Avian influenza virus has a hemagglutinin capable of binding what sialic acid type? What is the implication?
-binds a2,3 sialic acid=
infection of distal bronchiole/ type 2 pneumos
Role of birds in the spread of influenza
- act as RESOVOIRS for all flu strains
- rarely spread infection to humans directly
Role of pigs/ swine in the spread of influenza
can be infected by both human/ avian viruses; can be the site of REASSORTMENT= MIXING VESSELS
Does “swine” flu infect humans?
Does “avian” flu infect humans?
- swine flu can infect pigs + birds + humans
- avian flu can infect humans, but it usually does not
Specifically, what determines an influenza subtype’s ability to disseminate (vs remaining in the respiratory tract)?
-number of amino acids in the HA cleavage site
A single basic amino acid in the HA cleavage site implicates what for a certain strain of influenza?
- extracellular cleavage only
- virus stays in respiratory tract
Multiple basic amino acids in the HA cleavage site implicates what for a certain strain of influenza?
-can be cleaved intracellularly
-can spread systemically
more amino acids –> able to bind more than one sialic acid receptor
2 exact functions of neuroamidase?
How are these functions carried out?
- facilitates release of virion progeny
- prevents aggregation of virus in extracellular space
*cleaves sialic acid from glycoproteins
Typical incubation period for influenza?
Is it assc with viremia?
1-3 days; NO assc viremia
4 complications of influenza
- otitis media
- sinusitis
- primary viral pneumonia (rare)
- secondary bacterial pneumonia (common)
Influenza patients are susceptible to infection by what other bugs?
#1 strep pneumo also: staph aureus, H. flu
What drug do you AVOID when treating influenza in kids?
Aspirin + fever in kids = Reyes
rash & puking –> encephalopathy & fatty liver
Four drugs for treating influenza:
Which 2 are the better 2?
If you shoot AROZ (arrows) laced with medicine into the lungs of someone with the flu, theyll get better!
- Amantadine
- Rimantadine
- Oseltamivir
- Zanamavir
Dr. OZ are the two actually being used. AROZ aren’t logical.
Amantadine and Rimantadine:
MOA
Flu class is treats
Why it isn’t used
M2 inhibitors; prevent viral uncoating
- only treats type A!
- prevents symptoms and titers if given w/in 48 hours of symptom onset BUT it PROMOTES RESISTANCE!
Oseltamavir and Zanamavir
MOA
Flu class it treats
Why is it used?
NA inhibitor
treats type A & B
good for preventing secondary bacterial infection;
less likely to promote resistance
Two types of immuno responses to flu?
neutralizing antibodies; cytotoxic T cells (CD8)
Flu Ab’s:
- What type of Ig are produced?
- what are they targeted against?
- What is their function?
- How long do they last?
- are they strain specific?
- IgA (nasal) and IgG/ IgM (serum) are produced
- Targeted against HA
- block infection
- last ~ 6 mos
- strain specific; immune to one straight doesn’t = immune to others
Flu CD8+ cells:
- What are they targeted at?
- What is their function
- How long do they last?
- Are they strain specific?
- targeted against any of the 5 key proteins (HA, NA, M2// M1, NP)
- Terminate replication; aid in disease recovery
- Half life= 4 years
- Can cross react if specific for M, NP proteins
2 reasons of immunization against influenza must be annual
drift/ shift; protective immunity is short lived
What strains do flu vaccines contain?
Those that circulated at the end of the previous season
Types A and B
Two ADRs to flu vaccines
egg allergy; Guillan Barre
Three types of flu vaccine
- whole virus (fixed/ inactivated)
- Split viruses (subvirons)
- purified glycoproteins
I had a test question on this somewhere:
Why specifically can influenza virus cause pandemics?
What part of its structure makes this possible?
The fact that it is SEGMENTED makes it easier for genome exchanges.
