Pandemic Flu

Question 1

What is the name for the family of 6 virus genera that cause flu?

Answer 1

Orthomyxoviridae

Question 2

Which 3 flus affect humans, and at what time of year do they tend to peak?

Answer 2

Influenza A (H1) - Beginning of January
Influenza A (H1N1) - End of December
Influenza B - March

Question 3

Targeted populations receive a flu vaccination, but what does this contain?

Answer 3

Trivalent vaccine (ie targets all 3 types of flu)
Contains a purified fraction with HA and NA of inactivated viruses

Question 4

Which animal is a natural reservoir of influenza A?

Answer 4

Ducks

Question 5

Why is human to human transmission of bird flu (H5N1) difficult?

Answer 5

Virus does not replicate well in cold temp of upper airways (~32C)
Does better in deeper lung tissue (~41.5C) but from here it is difficult to escape)

Question 6

Describe the genetic material (type/quantity) of the influenza virus

Answer 6

8 segments of negative-sense RNA, each piece containing either one or two genes.

Segments = nucleocapsid protein (unit of viral structure, consisting of a capsid with the enclosed nucleic acid.)

Very prone to mutation

Question 7

Influenza A virus strains are named according to their HA and NA types, but what do these abbreviations stand for?

Answer 7

HA = haemogglutinin activity
NA = neuraminidase activity

Haemogglutinin and neuraminidase are proteins on the surface of the viral envelope

Question 8

What is the role of haemogglutinin?

Answer 8

Causes agglutination of RBCs/URT (?upper resp tract) cells

Binds sialic acid receptors, allowing virus entry. Endosomal-viral envelope fusion = release

Question 9

What is the role of neuraminidase (aka sialidase)?

Answer 9

Cleaves the glycosidic bonds of the monosaccharide neuraminic/sialic acid, exposing receptors on host cell and disrupting mucin barrier

Question 10

What is antigenic drift?

Answer 10

A mutation to HA/NA, giving new strains of a virus

Question 11

What is antigenic shift?

Answer 11

A complete change of HA/NA type; can only occur in influenza A

Question 12

How does antigenic shift occur?

Answer 12

RNA segments are traded between human and animal strains of the virus

Question 13

Describe the pathogenesis of flu

Answer 13

Cleavage of influenza HA by clara tryptase in the lung leads to extended tropism/growth for H5 and H7

Question 14

List 4 causes of severe outcomes from flu

Answer 14

Secondary bacterial pneumonia
Mutant virus
Co morbidity
Cytokine storm

Question 15

Name 2 antivirals used to treat flu

Answer 15

Amantadine (influenza A only)

Neuraminidase inhibitors: Oseltamivir (Tamiflu), zanamivir (Relenza), sialic acid

Question 16

Describe the method of action of amantadine

Answer 16

Targets M2 ion channel, preventing viral replication

Question 17

What is a problem with the M2 inhibitors (eg amantadine)?

Answer 17

A single AA mutation (S31N) in the M2 gene confers resistance against these drugs.

The mutation now exists in many flu strains including H1N1

Question 18

When must neuraminidase inhibitors be given in order to be effective?