Lecture 10 Influenza Flashcards

(55 cards)

1
Q

What symptoms do influenza viruses mainly cause in humans ?

A

Respiratory
Non-respiratory

Generally fever with cough or sore throat

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2
Q

What 3 things make up a virus ?

A
  1. Genetic material (DNA or RNA)
  2. Protein coat
  3. And/or an envelope derived from host cell membrane
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3
Q

What kind of parasite is a virus?

A

Obligate intracellular parasite
(Only reproduce within living cells)

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4
Q

3 words to describe a virus

A
  1. Simple
  2. Miniscule
  3. Infectious
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5
Q

Each virus has a host range. What does the term host range mean?

A

Limited range of animals which can be infected

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6
Q

What do viruses have to do to immune system to cause disease ?

A

All animals have a strong immune system so virtudes have to antagonise these responses to be able to cause disease

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7
Q

General properties/structure of influenza A virion (5)

A
  1. Mainly spherical
  2. Enveloped
  3. ssRNA (-)sense
  4. Replication in the nucleus
  5. Segmented genome (8 segments, n=8)
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8
Q

What are the 3 surface proteins of influenza A virion?

A
  • Haemagglutinin (HA)
  • Neuraminidase (NA)
  • Matrix protein 2 (M2)
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9
Q

What does Haemagglutinin (HA) do? (3)

A
  • Binds to sialic acid receptors and allows virus to enter into host cell
  • Agglutinates red blood cells
  • Antigenic (neutralising)
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10
Q

What does NA do ? (3)

A
  • Cleaves sialic acid to release virus
  • Degrades mucin (allows virus to get closer to cells so HA can bind to cells)
  • Antigenic (non-neutralising)
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11
Q

What does Matrix protein 2 (M2) do?

A
  • Forms proton channel that facilitates uncoating and assembly of the virion
  • Stabilises the virus budding
  • Antigenic (neutralising)
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12
Q

Outer lipid envelope of influenza A virion (2)

A
  • lipid bilayer from plasma membrane of infected host cell
  • supported by the M1 protein, which play role virion assembly
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13
Q

Nucleocapsid of influenza virus

A

RNA along with 4 different proteins

  • each nucleocapsid is of 8 different single stranded RNA + nucleoprotein (NP) and RNA polymerase (polymerase basic protein 1 (PB1) and 2 (PB2) and acid protein (PA)).
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14
Q

How many different serotypes of influenza are there? Name them

A

4 different serotypes

Influenza: A, B, C, D

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15
Q

How do the serotypes of influenza differ? (3)

A
  • They are A, B, C, D according to their internal structure proteins (nucleocapsid and matrix)
  • therefore these proteins can’t cross react
  • antibodies for influenza A will not help defend against influenza B
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16
Q

Epidemic

A

Rapid spread of infection in a city, state or entire country over a short period of time

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17
Q

Pandemic

A

An epidemic that spreads across borders, even worldwide, affecting large numbers

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18
Q

Characteristics of Influenza A
(What it infects, severity of infection, capability of causing epidemics)

A
  • Infects: human, swine (pig), birds, horses, bats, dogs
  • Severe clinical diseases
  • Most capable of unleashing epidemics and pandemic
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19
Q

Characteristics of Influenza B

A
  • Infects: human, seals
  • Generally mild but could be severe
  • Generally cause only milder pandemics
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20
Q

Characteristics of Influenza C

A
  • Infects: human, swine, dogs
  • only mild or asymptomatic
  • doesn’t cause epidemics or pandemics
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21
Q

What does influenza D infect ? (2)

A

Swine and cattle

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22
Q

What 2 surface glycoproteins are used to subtype the virus ?

A

Influenza viruses are named by specific HA and NA subtypes

E.g. H3N2

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23
Q

How many different HA and NA subtypes are there?

A
  • 18 HA types
  • 11 NA types

(n=198 different combinations)

24
Q

Few subtypes have caused human epidemics/pandemics. Name all 5 of them. Which 2 are used in vaccine?

A

H1N1, H2N2,H3N2, H5N1, H7N8

25
Name 4 different influenza pandemics
- Spanish flu - 1918 - Asian flu - 1957-58 - Hong Kong flu -1968-69 - Swine flu -2009
26
What types of influenza do seasonal vaccines protect us from?
Influenza A and B
27
What are the 6 stages of influenza virus replication cycle ?
1. Attachment 2. Uncoating 3. Transcription 4. Replication 5. Assembly 6. Budding
28
How long does the influenza viruses replication cycle take
8 hours
29
What happens during attachment (2)
- HA binds to sialic acid on host cell - virus is endocytosed; vesicle membrane and transferred to endosome
30
What happens during uncoating?
Endsosome acidification: - M2 increased H+ which leads to uncoating
31
What happens during transcription of the virus ?
Nucleocapsid goes to the nucleus and is transcribed mRNA are translated into proteins in cytoplasm
32
What happens during replication ?
The vRNP (-s) converts cRNP (+s), then through replication generates vRNP (-s) which go to cytoplasm
33
Assembly of virus
HA/NA transported to cell surface with M1 and genome segments
34
Budding of virus
Virus buds off by NA
35
What is the major determinant of host specificity and pathogenicity? And what does this mean
HA It determines how many different types of animal infected by virus
36
What is the structure of Haemagglutinin in influenza virion
- exists as a trimer in influenza virion
37
Each monomer of Haemagglutinin possesses 2 important sites, what are the 2 important sites?
- The receptor binding site - The cleavage site
38
What are the roles of the receptor binding site and cleavage site in HA?
- receptor binding site - confers host specificity - cleavage site - where the single chain of HA is cut into 2 chains At the N terminus it is fusion peptide which is critical for infectivity
39
Different forms of sialic acid are preferred by different viruses. What SA do human viruses and what SA do avian viruses preferentially bind to?
1. Human viruses - alpha 2,6 linked SA 2. Avian viruses - alpha 2,3 linked SA Swine act as a mixing vessel
40
What are the 2 different forms of sialic acid receptor?
1. N-acetylneuraminic acid- alpha2,6 linked galactose (alpha 2,6 linked) 2. N-acetylneuraminic acid- alpha2,3 linked galactose (alpha 2,3 linked)
41
What are the 2 mechanisms which the influenza virus keeps changing by?
1. Antigenic drift 2. Antigenic shift
42
What is antigenic drift in influenza. What types of influenza does it affect?
- minor changes in antigenic sites of the HA and NA because of: - error prone replication - no proofreading - provides selective advantage: seasonal flu (epidemics) - Influenza A, B and C
43
What is antigenic shift ?
- major changes due to a re-assortment of genes that occurs when 2 different influenza viruses infect the same host
44
Why does antigenic shift occur? (2)
- segmented genome - wide host ranges
45
What does antigenic shift cause and what type of influenzas does it occur in?
- causes complete change of HA, NA or both - only occurs in influenza A - usually requires non-human intermediate
46
What does the current vaccine for influenza help against?
Influenza A and B **but not C**
47
How vaccine strain selected
48
Treatment for viral infections/viruses
Antivirals
49
What are the 2 types of antivirals ?
1. Adamantanes 2. Neuraminidase inhibitors
50
Give 2 examples of adamantanes ?
- Amantadine - Rimantadine
51
What do adamantanes do
- M2- ion channel inhibitors - block viral uncoating - treatment or prophylaxis - CNS and anticholinergic effect, tetragenic - **treats influenza A only**
52
Why are viruses becoming more resistant to adamantanes ?
- the gene for M2 is susceptible to mutations so strains developing resistance
53
Give 2 examples of Neuraminidase inhibitors
1. Oseltamivir 2. Zanamavir
54
What type of influenzas do Neuraminidase inhibitors treat?
Influenza A and B
55
Features of Neuraminidase inhibitors (5)
1. Generally well-tolerated, some cause nausea/vomit 2. Most effective within 48hr of onset 3. Relief from symptoms for 1-2 days or less 4. Treatment or prophylaxis (oseltamivir) 5. Oral or inhaled (zanamavir)