INF2 - E. RESPIRATORY VIRUSES-COVERED

Question 1

what viruses cause colds

Answer 1

• rhinoviruses (normally harmless)
• adenoviruses
• influenza (causes epidemics)
• coronaviruses (SARS and MERS)

Question 2

how are colds and flus transmitted

Answer 2

• airborne droplets
• direct contact with nasal secretions
• fomites

Question 3

what are the 3 genera of influenza viruses

Answer 3

1. influenza A infects humans, horses, pigs, other mammals, birds
   - most serious
   - seasonal epidemics and flu pandemics
2. influenza B infects humans and seals
   - seasonal epidemics
3. influenza C infects humans, pigs, dogs
   - mild resp symtpoms

Question 4

features of influenza viruses

Answer 4

• enveloped
• (-)ssRNA (baltimore group 5)
• 100nm

spikes:
- haemagglutinin (HA)
- neuraminidase (NA)

Question 5

influenza genome

Answer 5

• 8 separate (-)ssRNA molecules

Question 6

how are influenza A viruses categorised into subtypes

Answer 6

• based on HA and NA proteins on their surface

more than 16 antigenically different HA subtypes (H1 to H16)
more than 9 distinct NA subtypes (N1 to N9)

• antibodies to one subtype don’t react with another subtype
• H1-16N1-9
• therefore always need to make new vaccines
• what subtypes most prevalent

Question 7

influenza strains nomenclature rules

Answer 7

1. influenza type (A,B,C)
2. species from which isolated (unless human - no speccies)
3. place of isolation
4. strain designation
5. year isolation
6. (HxNx) subtype (for influenza A only)

ie
A/perth/16/2009 (H3N2) - FROM HUMAN
C/Mie/199/2012

vaccine lists these
usually has 4 strains

Question 8

zoonotic influenza strains

Answer 8

• swine flu (H1N1) - PIG TO HUMANS
• avian flu (H5N1) - BIRD TO HUMANS

Question 9

will you have immunity to other subtypes if infected by one subtype

Answer 9

NO

Question 10

attachment and entry of influenza

Answer 10

• HA protein attaches to sialic acid on epithelial cell surface in upper resp tract
• followed by uptake into endosomes

Question 11

sialic acid

Answer 11

• attached to a galactose molecule in an alpha-(2,3) glucosidic bond

Question 12

selectivity of influenza viruses

Answer 12

• human influenza viruses bind alpha-2,6 configuration
• avian influenza viruses bind alpha-2,3 configuration
• pigs have either type of linkage so they are susceptible to human and avian flu virus

Question 13

zoonotic influenza: genetic exchange

Answer 13

• genetic exchange between influenza viruses from different hosts creates new subtypes = antigenic shift

Question 14

antigenic shift

Answer 14

• more deadly
• mixing of genetic material
• helps the flu virus invade our immune system and keep on making us sick each year

Question 15

antigenic drift

Answer 15

• mutations where our antibodies would bind to neutralise virus

Question 16

uptake of influenza virus in endosomes

Answer 16

• endosome has proton pumps which decrease endosomal pH from 7 to 5
• M2 ion channel is a proton pump which channels the protons into virion, lowering pH
• result is fusion of viral envelope with endosomal membrane and release of viral genome into cytoplasm

Question 17

fusion of influenza virus

Answer 17

• HA attaches to sialic acid, mediates fusion of envelope with endosomal membrane as pH decreases
• NA enables viral release from host cell by cleavage sialic acid on host cell and from mucin to allow access to new target cells

Question 18

example of a M2 ion channel blocker

Answer 18

Amantadine
- used in Parkinson’s swell
- blocks M2 ion channel
- no fusion with endosomal membrane

Question 19

sialic acid mimic drugs: neuraminidase inhibitors

Answer 19

• mimics NA natural ligand sialic acid
• sialic acid can’t bind to NA on virus
• block viral escape from infected cells
• relenza and tamiflu

Question 20

rhinoviruses

Answer 20

• naked
• receptors for human rhinovirus:
  ICAM-1 and LDLR on resp epithelial cells

Question 21

adenovirus

Answer 21

• naked
• receptors in upper resp tract:
  CAR, CD46, integrins recognising RGD loop