5 - Influenza Virus

Question 1

what is a virus?

Answer 1

• 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

Question 2

structure of influenza A virion: general properties

Answer 2

• mainly spherical
• enveloped
• ssRNA (-)sense
• replication in the nucleus
• segmented genome (n=8)

Question 3

which proteins are on the surface of influenza A

Answer 3

Haemagglutinin (HA)

Neuraminidase (NA)

Matrix protein 2 (M2)

Question 4

Haemagglutinin (HA)

Answer 4

• binds sialic acid receptors = viral entry
• agglutinates RBCs
• antigenic (neutralising)

Question 5

Neuraminidase (NA)

Answer 5

• cleaves sialic acid to release virus
• degrades mucin
• antigenic (non-neutralising)

Question 6

Matrix protein 2 (M2)

Answer 6

• forms proton channel that facilitates uncoating and assembly
• stabilises the virus budding
• antigenic (neutralising)

Question 7

envelope and interior of influenza A

Answer 7

has an outer lipid envelope and nucleocapsid

Question 8

outer lipid envelope of Influenza A

Answer 8

• lipid bilayer from plasma membrane of infected host cell

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

Question 9

nucleocapsid of Influenza A

Answer 9

• each of 8 different single stranded RNA + nucleoprotein (NP) + RNA polymerase (PB1, PB2 and PA)

Question 10

types and characteristics of influenza viruses

Answer 10

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

Question 11

epidemic

Answer 11

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

Question 12

pandemic

Answer 12

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

Question 13

antigenic structure and classification

Answer 13

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)

Question 14

which subtypes have caused human epidemics/pandemic

Answer 14

H1N1, H2N2, H3N2, H5N1, H7N8,

Question 15

which 4 pandemics have been caused by influenza virus?

Answer 15

• spanish flu (1918) (H1N1)
• Asian flu (1957/8)(H2N2)
• Hong Kong Flu (1968/9)(H3N2)
• Swine Flu (2009)(H1N1)

Question 16

influenza replication cycle

Answer 16

attachment, uncoating, transcription, replication, assembly, budding

Question 17

what happens in the attachment stage?

Answer 17

HA-Sialic acid on host cell

- virus endocytosed; vesicle membrane and transferred to endosome

Question 18

what happens in the uncoating stage?

Answer 18

Endosome acidification - M2 increased H+ = uncoating

Question 19

what happens in the transcription stage?

Answer 19

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

Question 20

what happens in the replication stage

Answer 20

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

Question 21

what happens in the assembly stage

Answer 21

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

Question 22

what happens in the budding stage?

Answer 22

Virus buds off by NA

Question 23

role of HA

Answer 23

exists as a trimer in the virion

possesses 2 important sites

• receptor binding site + cleavage site

Question 24

what is the receptor binding site?

Answer 24

confers host-specificity

Question 25

what is the cleavage site

Answer 25

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

Question 26

what are the 2 versions of the sialic acid receptor?

Answer 26

α2,6 linked - human viruses α2,3 linked - avian viruses

Question 27

which 2 mechanisms allow influenza to change its structure

Answer 27

antigenic drift and antigenic shift

Question 28

what is antigenic drift

Answer 28

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

Question 29

what is antigenic shift

Answer 29

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

Question 30

Adamantanes

Answer 30

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).

Question 31

Neuraminidase inhibitors

Answer 31

- 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)