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Infection and immunity > 21. Influenza > Flashcards

21. Influenza Flashcards

1
Q

what is the structure of the influenza genome?

A

segmented negative sense RNA genome

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2
Q

what are the 3 influenza viruses?

A

influenza A
influenza B
influenza C

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3
Q

which is the most important influenza virus?

A

influenza A

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4
Q

why do the influenza vaccines need to be updated every year?

A

due to the antigenic drift of influenza

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5
Q

how can a significantly different influenza strain appear?

A

genetic reassortment called antigenic shift
these can evade all pro-existing immunity

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6
Q

What is commonly confused with influenza?

A

a bad cold but none are as bad as influenza

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7
Q

what are the symptoms of influenza?

A

headache
fever
cough
joint and muscle ache
fatigue
recover in about 2 weeks

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8
Q

who are the most vulnerable to influenza?

A

the very young and the very old

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9
Q

what commonly kills you when you have influenza?

A

a secondary bacterial pneumonia infection

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10
Q

how many influenza deaths are there in a typical year in the UK?

A

10,000-12,000

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11
Q

how many influenza deaths are there in an epidemic year in the UK?

A

20,000-30,000

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12
Q

how many people did the spanish flu kill?

A

over 40 million
more then WW1 and WW2 combined

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13
Q

how many genome segments does influenza have?

A

8 segments

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14
Q

how many proteins does influenza produce?

A

10 classical flu proteins
additional proteins produced by reassorment tricks

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15
Q

what are the components of the influenza virus particle?

A

membrane from infected cell
H protein
N protein
M1 matrix
M2 ion channel
genome segments

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16
Q

what are the influenza genome segments associated with?

A

3 virally coded replicated proteins
Nucleocaspid protein coating the length of RNA

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17
Q

what does the M2 ion channel do?

A

pumps H+ ions from outside the virus to inside

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18
Q

what are the H and N proteins

A

membrane glycoproteins - antigens

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19
Q

what does the M1 matrix protein do?

A

keep contact between the H and N glycoproteins and the genome protein complexes

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20
Q

How does influenza enter and infect the host cell?

A
  1. attaches to sialic acid residues by the H protein
  2. taken into an endosome which becomes acidified
  3. the drop in pH causes changes in the H protein and causes fusion of the virus and endosome membranes
  4. H+ enter the virion through M2 and causes RNA to be released and move to the nucleus
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21
Q

why is the H protein critical for endosomal membrane fusion?

A

drop in pH causes conformational changes in H protein that exposes sequences to attach to the endosome membrane

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22
Q

what is unusual about influenza as an RNA virus?

A

it replicates in the nucleus

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23
Q

what is each strand of the RNA genome associated with?

A

nucleocaspid proteins and replication proteins like RdRp

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24
Q

what does the RdRp make from the -ve sense ssRNA genome?

A

mRNA for transcription
a cRNA anti-genome for replication

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25
Q

where is all the coding information on a -ve sense ssRNA virus?

A

all the info is on the opposite strand including the start codon

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26
Q

how is the mRNA different from the anti-genome?

A

when making mRNA the RdRp detects a stop codon and poly adenylates the strand and other modifications
the cRNA anti-genome is a faithful copy of the genome

27
Q

how does influenza generate more proteins then it has segments?

A

some influenza mRNA can be alternativly spliced which is why it must enter the nucleus

28
Q

what carries out influenza mRNA alternative splicing?

A

the host cell’s splicing mechanisms

29
Q

what happens when the new viral proteins appear on the cell membranes?

A

It makes them visible to the host immune system

30
Q

what viral proteins are exported back to the host nucleus?

A

viral replication proteins to replicate the viral genome and export them to the new virions

31
Q

what is the main influenza antigenic proteins the host recognises and produces antibodies to?

A

H (heamagglutanin)

32
Q

what is the role of the influenza N protein?

A

destory the sialic acid in the host cell membrane so the virus doesn’t reinfect the same cell

33
Q

how many know serotypes of H and N are there?

A

H = 15
N = 9

34
Q

why do different influenza serotypes cause a problem for the host?

A

antibodies would only work against the same serotype so not much protection from reinfection

35
Q

what causes antigenic drift?

A

occasional mistakes during genome replication and lack of proofreading
the viral progeny will have altered genes and some lead to changes on the H and N surface proteins

36
Q

what can mutations in the genome do?

A

make the virus more effective and avoid the immune system
make the virus less effective or dead

37
Q

what is the limitation of antigenic drift?

A

the virus structure needs to be able to tolerate alterations to its structure to able to survive the mutation
some viruses like measles cannot tolerate structural mutations

38
Q

How does antigenic drift effect immunity?

A

some but not all of initially generated antibodies can recognise the strain
reducing the population immunity

39
Q

what makes influenza vaccines useless after 4/5 years?

A

antigenic drift and the H protein’s ability to tolerate changes and be functional
these over a few years significantly reduce effectiveness

40
Q

what other animals can influenza A infect?

A

horses
pigs
ferrets
birds

41
Q

what is the mixing pot of influenza?

A

pigs

42
Q

why are pigs the mixing pot for influenza A?

A

both human and bird influenza strains can infect pigs

43
Q

how do influenza strains mix in pigs?

A

some cells in the pig will be infected with both the bird virus and the human virus
the compatible segments of the genomes can mix in the new virion particles
Doesn’t happen readily due to compatibility

44
Q

what else can mix with the human and avian influenza strains?

A

native pig influenza strains

45
Q

What is antigenic shift?

A

random genetic reassortments between the H and N genes on separate segments

46
Q

what can influenza antigenic shift result in?

A

A virus that:
can infect and replicate well in humans
are antigenically different from other influenza that has been recently seen

47
Q

what do antigenically shifted viruses usually result in?

A

a new epidemic/pandemic of influenza

48
Q

what possibly was the 1890 flu pandemic?

A

a bovine coronavirus

49
Q

what are the 2 alternate mixing pot ideas?

A
  1. an avian influenza adapts through zoonosis to infect humans
  2. the avian influenza and human influenza infect the same human at the same time and reassortment occurs
50
Q

what usually limits avian influenza when jumping straight to humans?

A

they cannot sustain person to person spread
it is a worry that avian influenza could develop this and trigger a pandemic

51
Q

what are the 3 routes influenza could take to become a pandemic strain?

A
  1. reassortment when an avian virus infects a person already infected with human influenza
  2. an intermediate animal (pig) could contract both at the same time
  3. an avian influenza might adapt through random mutation and acquire the ability to infect person to person
52
Q

where are the 4 main WHO influenza monitoring labs?

A

london
atlanta, USA
tokyo
melbourne

53
Q

what does WHO do when monitoring influenza?

A

recieve information about concerning strains
make yearly reports
Recommend strains to be included in the annual vaccine

54
Q

what is the biggest limitation of the yearly influenza vaccine?

A

they have to decide what strains to included in march/april so they can be produced in time
it can be difficult to predict what the dominant strains will be

55
Q

what are the 4 types of influenza vaccine?

A

inactivated virus (whole dead virus)
split vaccine (whole purified virus killed with detergents)
sununit vaccine (purified HA and N proteins)
Live attenuated influenza vaccine

56
Q

how does the live attenuated influenza vaccine work?

A

the virus is modified to grow at the temperature of the nose and not the lungs
creates localised immunity and mucosal immunity

57
Q

what is currently the most common influenza vaccine?

A

split vaccine

58
Q

what is thought to be a good new influenza target?

A

M2 protein external region called M2e

59
Q

why use M2e as a vaccine target?

A
  1. part of the H+pump
  2. M2e region hasnt changed since 1918
  3. shares gene with M1 so has very limited tolerance to mutation without knocking out both gene functions
  4. M2e appears on the host membrane earlier then other proteins
60
Q

why have we not considered M2e as a target before?

A

the immune system doesn’t naturally make antibodies to it as only a small part is external

61
Q

what do we need more understanding of to make better influenza vaccines?

A
  1. what parts of the virus rapidily change and what don’t
  2. what the body decides to make antibodies to and be able to manipulate it
62
Q

what current treatment do we have for influenza?

A

Tamiflu
Relenza
(amantadine and flumadine)

63
Q

how do current treatments for influenza work?

A

they inhibit different stages of the influenza replication cycle

64
Q

what are the disadvantages for influenza treatments?

A

have to be given in the first 2 days of infection
side effects
resistance can emerge very fast

Infection and immunity (22 decks)

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