#8 small group influenza

Question 1

Is influenza naked or enveloped? –

Answer 1

It is enveloped •

Question 2

What are the surface proteins? –

Answer 2

Hemagglutinin (HA), Neuraminidase (NA), and the M2 ion channel

Question 3

• What type of genome does influenza virus have?

Answer 3

– Eight (-) sense RNA genome

segments

Question 4

What is the receptor(s) for entry?

Answer 4

–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

Question 5

2-3 linkages for sialic acid are in

Answer 5

the lower respiratory tract

Question 6

2-6 linked sialic acid are in

Answer 6

upper respiratory tract

Question 7

What viral protein binds the receptors?

Answer 7

Hemagglutinin on the virus binds the sialic acid receptors

Question 8

Where does membrane fusion occur?

Answer 8

– In the endosome, triggered by low pH

Question 9

What viral protein(s) drives fusion and uncoating?

Answer 9

– Hemagglutinin drives membrane
fusion, the M2 ion channel is needed to release the genomic RNA/protein complexes
from the matrix to allow complete uncoating

Question 10

Hemagglutinin drives membrane
fusion, the ________is needed to release the genomic RNA/protein complexes
from the matrix to allow complete uncoating

Answer 10

M2 ion channel

Question 11

What polymerase makes viral mRNA?

Answer 11

–The virally encoded RNA polymerase that

enters the cell within the infecting virion

Question 12

What is a major challenge in assembling new virus particles?

Answer 12

– 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

Question 13

What are the targets of antiviral intervention? -

Answer 13

-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

Question 14

The M2 ion channel:_______ and_______ are steric inhibitors that ‘plug’ the channel. –

Answer 14

amantadine

rimantidine

Question 15

What is the mechanism for Tamiflu and zanamivir

Answer 15

– Neuraminidase: (Tamiflu) and zanamivir are competitive inhibitors that inhibit the enzyme and block release of mature virus from the cell surface

Question 16

What is a limitation of the antivirals?

Answer 16

Drug resistant viruses easily arise

Question 17

Distinguish the mechanism of genetic drift from genetic shift.

Answer 17

– Genetic drift results from the introduction of mutations into viral proteins by the error-prone viral polymerase. Genetic shift results from reassorting genome segments

Question 18

________ results from reassorting genome segments

Answer 18

Genetic shift

Question 19

________results from the introduction of mutations into viral proteins by the error-prone viral polymerase

Answer 19

Genetic drift

Question 20

Describe how genetic drift and shift alter seasonal flu and the appearance of pandemic strains.

Answer 20

– 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.

Question 21

_________ results in wholesale antigenic changes due to presence of a new genome segment.

Answer 21

Genetic shift

Question 22

__________ causes slow, gradual antigenic changes, requiring a new vaccine each year.

Answer 22

Genetic Drift

Question 23

How many strains are in the flu vaccine? –

How are the strains chosen?

Answer 23

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

Question 24

What is the primary method for producing flu vaccine strains?

Answer 24

–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

Question 25

What are the key features of the flu vaccine? How is it made?

Answer 25

• • 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

Question 26

What aspect of the patient’s history likely contributed to severe disease?

Answer 26

–The patient was immunosuppressed

Question 27

What is the significance of nasopharyngeal and bronchoalveolar lavage analysis?

Answer 27

-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

Question 28

What does this suggest about receptor use for H1N1?

Answer 28

– The virus can use alpha 2-3 sialic acid, which is typical of the lower respiratory tract

Question 29

What is the significance of the negative results of bacterial infection?

Answer 29

– Serious disease was the result of direct viral pathogenesis. Typically, serious disease from the seasonal flu results from secondary bacterial infections.