#8 small group influenza Flashcards
Is influenza naked or enveloped? –
It is enveloped •
What are the surface proteins? –
Hemagglutinin (HA), Neuraminidase (NA), and the M2 ion channel
• What type of genome does influenza virus have?
– Eight (-) sense RNA genome
segments
What is the receptor(s) for entry?
–The sialic acid moiety on glycoproteins: alpha 2-3 linked sialic acid in the lower respiratory tract, or alpha 2-6 linked sialic acid in the upperrespiratory tract
2-3 linkages for sialic acid are in
the lower respiratory tract
2-6 linked sialic acid are in
upper respiratory tract
What viral protein binds the receptors?
Hemagglutinin on the virus binds the sialic acid receptors
Where does membrane fusion occur?
– In the endosome, triggered by low pH
What viral protein(s) drives fusion and uncoating?
– Hemagglutinin drives membrane
fusion, the M2 ion channel is needed to release the genomic RNA/protein complexes
from the matrix to allow complete uncoating
Hemagglutinin drives membrane
fusion, the ________is needed to release the genomic RNA/protein complexes
from the matrix to allow complete uncoating
M2 ion channel
What polymerase makes viral mRNA?
–The virally encoded RNA polymerase that
enters the cell within the infecting virion
What is a major challenge in assembling new virus particles?
– Assuring that the new
particle has the 8 different genome segments. A virus with 8 segments, but not one of each, would not be infectious
What are the targets of antiviral intervention? -
-The M2 ion channel: amantadine and
rimantadine are steric inhibitors that ‘plug’ the channel. – Neuraminidase: oseltamivir (Tamiflu) and zanamivir are competitive inhibitors that inhibit the enzyme and block release of mature virus from the cell surface
The M2 ion channel:_______ and_______ are steric inhibitors that ‘plug’ the channel. –
amantadine
rimantidine
What is the mechanism for Tamiflu and zanamivir
– Neuraminidase: (Tamiflu) and zanamivir are competitive inhibitors that inhibit the enzyme and block release of mature virus from the cell surface
What is a limitation of the antivirals?
Drug resistant viruses easily arise
Distinguish the mechanism of genetic drift from genetic shift.
– Genetic drift results from the introduction of mutations into viral proteins by the error-prone viral polymerase. Genetic shift results from reassorting genome segments
________ results from reassorting genome segments
Genetic shift
________results from the introduction of mutations into viral proteins by the error-prone viral polymerase
Genetic drift
Describe how genetic drift and shift alter seasonal flu and the appearance of pandemic strains.
– Drift causes slow, gradual antigenic changes, requiring a new vaccine each year. Genetic shift results in wholesale antigenic changes due to presence of a new genome segment.
_________ results in wholesale antigenic changes due to presence of a new genome segment.
Genetic shift
__________ causes slow, gradual antigenic changes, requiring a new vaccine each year.
Genetic Drift
How many strains are in the flu vaccine? –
How are the strains chosen?
Usually three
–There is a worldwide surveillance network that tracks
virus prevalence, and the 3 strains to be included in the US vaccine are chosen by the
FDA based on what is in circulation and the anticipated strains for the coming season
What is the primary method for producing flu vaccine strains?
–Vaccine strains are primarily grown in chicken eggs, which give high titers, but take a long time to optimize and cannot be given to those with egg allergies. There is an egg shortage, which causes production problems. Cell-based virus growth is a new alternative
What are the key features of the flu vaccine? How is it made?
- Features:
i) grows well,
ii) displays desired surface antigens,
iii) safe. – Production: Academic labs receive the wild strains, and take advantage of ‘reassortment’ with laboratory strains to select for viruses that have the HA and NA surface proteins of the desired vaccine, but the ‘safe’ genes of the lab-adapted strain that grows well and is much less pathogenic
- Features:
What aspect of the patient’s history likely contributed to severe disease?
–The patient was immunosuppressed
What is the significance of nasopharyngeal and bronchoalveolar lavage analysis?
-There was little virus in the upper respiratory tract, and appearance of virus in the lower respiratory tract correlated with onset of severe disease: the ability of the virus to replicate in the lower respiratory tract contributed to pathogenesis
What does this suggest about receptor use for H1N1?
– The virus can use alpha 2-3 sialic acid, which is typical of the lower respiratory tract
What is the significance of the negative results of bacterial infection?
– Serious disease was the result of direct viral pathogenesis. Typically, serious disease from the seasonal flu results from secondary bacterial infections.
