5 - Influenza Virus Flashcards

1
Q

what is a virus?

A
  • A simple, miniscule, infectious,
  • obligate intracellular parasite (only reproduce within living cell)
  • comprising of genetic material (DNA or RNA)
  • surrounded by a protein coat
  • and/or an envelope derived from a host cell membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

structure of influenza A virion: general properties

A
  • mainly spherical
  • enveloped
  • ssRNA (-)sense
  • replication in the nucleus
  • segmented genome (n=8)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

which proteins are on the surface of influenza A

A

Haemagglutinin (HA)

Neuraminidase (NA)

Matrix protein 2 (M2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Haemagglutinin (HA)

A
  • binds sialic acid receptors = viral entry
  • agglutinates RBCs
  • antigenic (neutralising)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Neuraminidase (NA)

A
  • cleaves sialic acid to release virus
  • degrades mucin
  • antigenic (non-neutralising)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Matrix protein 2 (M2)

A
  • forms proton channel that facilitates uncoating and assembly
  • stabilises the virus budding
  • antigenic (neutralising)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

envelope and interior of influenza A

A

has an outer lipid envelope and nucleocapsid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

outer lipid envelope of Influenza A

A
  • lipid bilayer from plasma membrane of infected host cell

- supported by the M1 protein, which play role in virion assembly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

nucleocapsid of Influenza A

A
  • each of 8 different single stranded RNA + nucleoprotein (NP) + RNA polymerase (PB1, PB2 and PA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

types and characteristics of influenza viruses

A

4 different serotypes: A,B,C,D according to internal structure proteins
- these proteins can’t cross-react

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

epidemic

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

pandemic

A

an epidemic that spreads across boarders, even worldwide, affecting large numbers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

antigenic structure and classification

A

Two surface glycoproteins are used to subtype the virus

  • Influenza viruses are named by specific HA and NA subtype: (e.g. H3N2)
  • 18 HA types and 11 NA types (n=198 different combinations)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

which subtypes have caused human epidemics/pandemic

A

H1N1, H2N2, H3N2, H5N1, H7N8,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

which 4 pandemics have been caused by influenza virus?

A
  • spanish flu (1918) (H1N1)
  • Asian flu (1957/8)(H2N2)
  • Hong Kong Flu (1968/9)(H3N2)
  • Swine Flu (2009)(H1N1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

influenza replication cycle

A

attachment, uncoating, transcription, replication, assembly, budding

17
Q

what happens in the attachment stage?

A

HA-Sialic acid on host cell

- virus endocytosed; vesicle membrane and transferred to endosome

18
Q

what happens in the uncoating stage?

A

Endosome acidification - M2 increased H+ = uncoating

19
Q

what happens in the transcription stage?

A

nucleocapsid goes into the nucleus and transcribed mRNA are translated into proteins in cytoplasm

20
Q

what happens in the replication stage

A

the vRNP (-s) converts to cRNP (+s), then through replication generates vRNP (-s) -> cytoplasm

21
Q

what happens in the assembly stage

A

HA/NA transported to cell surface with M1 and genome segments

22
Q

what happens in the budding stage?

A

Virus buds off by NA

23
Q

role of HA

A

exists as a trimer in the virion

possesses 2 important sites

  • receptor binding site + cleavage site
24
Q

what is the receptor binding site?

A

confers host-specificity

25
Q

what is the cleavage site

A

where the single chain is cut into two chains. At the N-terminus it is fusion peptide which is critical for infectivity

26
Q

what are the 2 versions of the sialic acid receptor?

A

α2,6 linked - human viruses

α2,3 linked - avian viruses

27
Q

which 2 mechanisms allow influenza to change its structure

A

antigenic drift and antigenic shift

28
Q

what is antigenic drift

A

minor changes in the antigenic sites of the HA and NA, because of:

  • Error prone replication
  • No proofreading Provides a selective advantage: seasonal flu (epidemics) Influenza A, B, and C
29
Q

what is antigenic shift

A

major changes due to a re-assortment of genes that occurs when two different influenza viruses infect the same host. `This occurs due to:

  • Segmented genome
  • Wide host ranges

> Complete change of HA, NA or both

> Only occurs in Influenza A

> Usually, requires non-human intermediate

30
Q

Adamantanes

A

amantadine and Rimantadine are M2-ion channel inhibitors:

  • Blocks viral uncoating
  • Treatment or Prophylaxis
  • Influenza A only
  • CNS + anticholinergic effect, teratogenic
  • The gene for M2 is susceptible to mutations, so strains are developing resistance (90 % viruses are now resistant to this category).
31
Q

Neuraminidase inhibitors

A
  • Influenza A+B
     Generally well-tolerated, some nausea/vomit
     Most effective within 48h of onset
     Relief from symptoms for ~1-2 days or less
     Treatment or prophylaxis (oseltamivir)
     Oral or inhaled (zanamavir)