Influenza seminar Flashcards
(21 cards)
Which sialic acids do human and avian IAV HA bind and why?
Humans: alpha2,6
Most abundant in upper respiratory tract epithelial cells
Birds: alpha2,3
Most abundant in intestinal tract epithelial cells
Is IAV capped/polyadenylated? Mechanism?
Yes, both
Mechanism: cap-snatching from host mRNA
How can NA facilitate virus spread?
Hint: HA
Prevents non-productive binding of HA of new virions to receptors bearing sialic acid present in the viral glycoproteins and in the membrane of the infected cells.
What is antigenic drift related to influenza virus? How can it be caused?
Natural process. Mutations arise during replication in genes encoding Ag.
Gradually accumulating mutations (in HA and NA) due to error-prone vRdRp (makes missense mutations)-> evade Ab-mediated immunity.
Substantial drift can be caused by one/few aa substitutions adjacent to the functional sites in the head (not stalk) of HA.
Both IAV & IBV
What is antigenic shift related to influenza virus? How can it be caused?
Drastic changes in antigenicity of HA of circulating IAVs - reassortment
Caused by combination of the genomes of two/more viral subtypes to form a new subtype. Encodes Ab-binding sites of the original strains.
Associated with IAV pandemics (often associated with extinction of previous circulating strains)
Why is it difficult to design an universal IAV vaccine?
Antigenic shift.
Often targeted toward HA (or NA) protein. Binding to conserved stalk domain is weak.
Head domain easily accumulates mutations that allows the virus to avoid binding to Abs
What are the viral targets for the antivirals amantadine and rimantadine? How are they administered? Are they problematic?
Target: M2 ion channel of IAVs
Oral delivery
Resistancy among circulating IAVs -> not recommended
How can we manage acute influenza?
Supportive measures:
Symptomatic treatment, rehydration, treatment of complications (e.g., bacterial pneumonia).
Antiviral agents
Prevention of transmission from natural animal reservoirs to humans:
- Water treatment
- Indoor raising
- Biosecurity
(Quarantine, animal vaccination)
Mention 3 subtypes of IAV and 2 subtypes of IBV
IAV:
A/H1N1, A/H3N2, A/H5N1
IBV:
B/Yamagata, B/Viktoria
What was the main achievements of Brevig mission?
Discovered the 1918 flu virus.
Decoded + assembled genome
Reconstructed (and study) virus in a BSL3 lab
Why is the efficacy of the influenza vaccine low?
- Mismatch between components with the circulating influenza strains
- Vaccine candidates can accumulate mutations during propagation in cell culture, eggs, and small animals
- Age-related immune response
What is a pandemic?
Widespread occurrence of an infectious disease over a whole country or the world at a particular time.
IAV
What is an endemic?
Widespread occurrence of an infectious disease in a community at a particular time.
What is the nomenclature of IAVs?
Virus type
/geographic origin
/strain number
/year of isolation
(H type N type)
Example:
A/Oslo/INS219/2009(H1N1)
Which subtypes of IAV are circulating in humans?
H1N1
H3N2
Mention influenza virus proteins (+ functions) that are central for the counter-response of viruses toward the host immune response
NS1:
Binds host factors E3 ubiquitin-protein ligases
-> prevents RIG-I activation in cytoplasm and the IFN (and ISG) response.
Can prevent host mRNA synthesis, processing, and trafficking events.
Can target JAK-STAT pathway
PB1-F2 (nonstructural protein):
Suppresses MAVS activation, required for IFN induction.
PB2:
Also target MAVS
PA-x:
Endonuclease activity that can suppress host gene expression.
Describe the process of apoptosis after virus infection briefly
- Trigger: large amount of vRNA
- PRRs recognize vRNA and transduce signals to
anti-apoptotic Bcl-2 protiens. - Bcl-2 release their pro-apoptotic partners
- Pro-apoptotic proteins initiate MOMP
(Mitochondrial outer membrane
permeabilization), ATP degradation, and
caspase 3 activation. - Cell death
What does the valence of a vaccine mean? E.g., with the influenza vaccine
Number of virus types the vaccine provide protection against.
Trivalent:
Against 2 IAV (H1N1 and H3N2) and 1 IBV (Yamagata) strains
Quadrivalent vaccine:
2 IAV (H1N1 and H3N2) and 2 IBV (Yamagata and Victoria) strains
Which sample materials are recommended for diagnostics?
Naso-pharyngeal aspirate (highest sensitivity)
Naso-pharyngeal swab
Convalescent serum
How are viruses detected?
Higher sensitivity:
- Viral cultures: detailed characterization of
novel viruses, surveillance and monitoring.
Time consuming
- Reverse transcription PCR (RT-PCR): Highly
sensitive, specific, quick, incorporated into
multiple assays, used to subtype viruses.
Expensive
Poor sensitivity:
- Antigen detection (early phase) from naso-
pharyngeal aspirate/swab (Few minutes, low
cost, low sensitivity)
- Virus detection
- Antibody detection (late phase) from serum
Which parts of the virus life cycle does it exist host-directed anti-IAV agents against? Mention some examples
Entire life cycle can be targeted:
- Attachment
- Endocytosis
- Endosomal acidification
- Fusion and uncoating
- vRNP import
- Transcription and replication
- Translation and protein …
- Protein nuclear import/export
- Golgi trafficking and virus assembly
- Budding and release
Others:
- Lipid biosynthesis
- Signaling
- Inflammation
- Metabolism
