L21 - Influenza

Question 1

Which type of influenza virus is most important for public health?

Answer 1

Influenza A

Question 2

What do these figures represent?
1000 deaths
20,000 deaths
40 million deaths

Answer 2

1000 deaths - a ‘normal’ flu year
20,000 deaths - an epidemic year in the UK
40 million deaths - Spanish Flu outbreak

Question 3

Why do so many elderly people die after contracting influenza?

Answer 3

More at risk from potentially lethal infections such as pneumonia which actually kill them rather than the influenza

Question 4

Give 3 facts about the influenza viral genome.

Answer 4

Segmented (8 segs), RNA, negative-sense

Question 5

Does each segment code for one protein?

Answer 5

No. 6 segments code for one viral protein, and 2 segments code for 2 proteins each = 10 classical viral proteins. (additional minor proteins)

Question 6

List 5 components of the influenza virus structure and draw these.

Answer 6

H - haemagglutanin (HA) - surface protein
N - neuroaminidase (NA) - surface protein
M1 matrix - brings genomes together with viral membrane proteins
M2 ion channel - forms pores across membranes
Genome segment - associated with 3 virus coded replication proteins and an N protein which coats the RNA

Question 7

Do viruses make their own membranes?

Answer 7

No, they use the host’s

Question 8

Which cells in the body do influenza attach to?

Answer 8

Lung cells

Question 9

How is the virus particle taken up into the cell

Answer 9

Via an endosome

Question 10

What happens as a result of the natural drop in pH within the endosome.

Answer 10

H proteins refold, exposing a fusogenic peptide which embeds in the endosomal membrane. ALSO M2 channel allows H+ into viral particle causing genomes to dissociate from M1 matrix allowing them to be released.

Question 11

What happens after fusion of virus and endosome?

Answer 11

Viral genomes released and transported to the nucleus.

Question 12

The genome is always associated with which proteins?

Answer 12

Wrapped up in N protein (nucleocapsid). Replication proteins inc. RNA-dependent RNA polymerase.

Question 13

What must happen before translation.

Answer 13

The (negative sense) genome must be transcribed into mRNA

Question 14

What is an antigenome and what is its purpose.

Answer 14

Antigenomes are positive-sense and are used to produce progeny genomes (-ve sense)

Question 15

What is RNA-dependent RNA polymerase used for and which end of the RNA does it associate with?

Answer 15

1) Making mRNA
2) Making antigenomes
the protein associates with the 3’ end of the genome.

Question 16

Which end does the ribosome associate?

Answer 16

ALWAYS works in the 5’ to 3’ direction.

Question 17

How does the virus leave the infected cell?

Answer 17

Antigenomes and then progeny genomes are make in the nucleus. Progeny genomes exported from nucleus. mRNA made from genome and exported from nucleus. mRNA is translated into viral proteins which assemble around the progeny RNA and bud off from the cell surface.

Question 18

What are the main features of the H protein and how does it interact with mammalian cells?

Answer 18

It is the major attachment protein of influenza. It is the major antigenic determinant for the humoral response.
It interacts by binding sialic acid groups on surface proteins of mammalian cells.

Question 19

Is the N protein antigenic?

Answer 19

Yes but is less important in the humoral response.

Question 20

How many serotypes are there?

Answer 20

15 for H and 9 for N

Question 21

What causes antigenic DRIFT

Answer 21

Polymerase occasionally makes errors during replication of viral genome. Resulting in genomes different to the parent.

Question 22

What is the result of antigenic DRIFT

Answer 22

The new progeny viruses will have altered genes. The mistakes may lead to a change in the surface glycoproteins H and N.

Question 23

What timeframe does antigenic DRIFT work on?

Answer 23

Over 4-5 years the slow accumulation of minor changes may reduce the effectiveness of a vaccine enough to render it useless.

Question 24

How is influenza A passed among its animal hosts?

Answer 24

Human and bird influenza A strains can both infect pigs but not usually infect each other.

Question 25

What are the implication of a pig being infected with both avian and human influenza viruses?

Answer 25

Re-assortment between the 2 viruses can occur inside an individual pig cell giving rise to antigenic SHIFT

Question 26

What feature of the genome makes re-assortment and therefore antigenic SHIFT possible?

Answer 26

The fact that it is segmented and the H and the N proteins are on different segments.

Question 27

Why may reassortment lead to new epidemics or pandemics?

Answer 27

The ‘new’ viruses may be able to infect and replicate well in humans. AND they would be antigenically different to any other influenza virus the human population

Question 28

What are the 3 main routes that avian flu may turn into a pandemic strain?

Answer 28

1) Avian virus infects human already infected with human flu. Reassortment may result in a human version of the devastating H5 N1.
2) In intermediate animal ie. pig may contract both human and avian H5 N1 influenza –> reassortment
3) Avian H5 N1 adapts itself through random mutation and acquire the ability to infect humans. (eg. Spanish fli)

Question 29

What difficulties does the WHO face when advising flu vaccine production.

Answer 29

They must predict in March which strains will dominate that winter because the vaccine takes 6 months to make. Therefore sometimes antigenic drift means the vaccine will not be protective over the most dominant strains.

Question 30

Name the 4 mains types of vaccine indicating which is the most common and which is the newest.

Answer 30

Inactivated (killed with chemicals)
MOST COMMON = Split vaccine (disrupted by detergents) 
Subunit vaccine (purified preparations of the H and N proteins.
NEWEST = Live attenuated influenza vaccine (LAIV) - nasal spray used in children, may well replace split vaccine

Question 31

What are the 3 limitations of antiviral drugs such as Tamiflu, Flumadine, Amantadine and Relenza?

Answer 31

They must be given within 2 days of contraction on virus.
Resistance to RNA viruses arises quickly.
All have known side effects so are given only with good reason.

Question 32

Outline the new vaccine which may protect from all influenzas.

Answer 32

Based on external region (M2e) of M2 envelope protein as this has not changed since 1918.
Viable alterations are limited because its open reading frame overlaps with the M reading frame.