Emerging Viruses

Emerging virus

• new species

• new place

• new tropism/viral characteristics

  • tropism → infecting different cell type

5 stages of disease energence

1. Agent in animals only

2. Primary infection

   • Animals → small human %

   • NO SPREADING FROM PEOPLE TO PEOPLE

3. Limited outbreak

   • Humans can transmit viruses back to animals

4. Long outbreak

   • Epidemic

5. Exclusive human agent

   • Pandemic

Viral emergence from animals to humans

• Increased human contact

  • farming

  • hunting

  • pets

  • zoos

  • live markets

  • emergence becoming more common from domestic than wildlife

Spillback

humans transmitting virus to animals

• influenza → humans → pigs

  • pig acts as mixing vessel → gene reassortment of human and avain strains

  • jumps back to humans

• SARS-CoV-2

  • humans → mink → deer → humans

  • limited spread

• Animal → human transmission route not necessarily the same as human → human transmission route

Evolution → viral changes

• virus does NOT have to be evolve to become less pathogenic

• Viruses become more pathogenic

  • high transmission rates, new pathogenic feature

  • recombinant virus can become pantropic and transmissible

why dont all emerging viruses lead to pandemics?

R0 <1

• R0 → number of infections each infection will cause

• Restriction factors

  • innate immune factors

• Ecological factors

  • run out of susceptible hosts

• Human factors

  • infection control

  • e.g. quarantine, surveillance (10)/control zones (3)

  • radius km

• more infections → more opportunities to evolve and spread and change

What makes a virus more likely to emerge in pigs?

• Viral factors

  • mutations → viral attachment protein can increase tissue tropism

  • shed without clinical signs (asymptomatic) → easy to infect mammalian species → mammals have common receptors

• Environmental or Host factors

  • dense, crowded environment → rapid spread

  • more opportunity to adapt and increase transmission

  • biosecurity lapses (e.g. poor ventilation and hygiene)

  • sylvatic populations in close circulation (e.g. wild pigs, african swine fever)

Emerging Viruses riskier now?

• increased human population and contact with animals

• increased animal population (mass high density farming)

• habitat destruction → more contact with animals

• global interconnectivity → facilitates exponential spread

cross species transmission

• canine parvo

• influenza

canine parvovirus

• 98% related to fpv (feline panleuko)

  • did not jump straight from cat to dog → intermediate host (fox/raccoon) then jumped to dog

• capsid held tightly together

• environmentally stable

• difficult to remove from kennel

• capsid mutations determine host sensitivity

  • mutations in capsid allows adaptation to difference in dog transferin receptors

  • only viruses that had capsid mutations 93 and 323 grow well in dog cells

• cpv 2a wipes out cpv 2

  • additional change in capsid → cpv so mutated it can no longer reinfects cats → adapted to the extreme for canine receptors so it cannot bind to cat receptors

flu virus morphology

• 8 -ve sense ssrna segments

  • enables reassortment → subtypes

• surface proteins

  • H → haemagglutinin (spike)

  • N → neuraminidase

flu life cycle [8]

1. bind to host cell receptors → endocytosis

   • alpha 2,3 or alpha 2,6 linked sialic acid

2. uncoating of virus in vesicle

3. replication in NUCLEUS (even though rna)

4. RNA made

5. protein synthesis in cytoplasm

   • can skip straight to step 8

6. re-enters nucleus and then exits again

7. packaging and assembly

8. buds with envelope taken from host membrane → release

avian influenza

H1-16

N1-9

Oral/faecal transmission

Natural host for influenza A = WILD birds

B - just for humans

human flu

• H1N1

• H3N2

• flu B + C

• all respiratory

how does flu switch hosts (wild birds to poultry)

• Wild birds → poultry

  • low pathogenic → high pathogenic often requires ‘switch’

    • Switch → addition of multiple basic amino acids in cleavage site in HA gene

    • changes how HA is cleaved → change in pathogenicity

  • Low path → enteric and respiratory

  • high path → systemic

  • Increased path mutation → faster spread in flock

how does flu switch hosts (birds → humans)

• change in receptor binding

  • alpha 2,3 sialic acid (birds) changed to alpha 2, 6 sialic acid (humans)

    • pigs have both sialic acids → mixing vessels

    • mink/ferrets have similar receptors to humans in lungs → farming in high densities make them risky intermediate hosts

• Protein changes to different host factors

  • polymerase change to different ANP32 → protein used for viral transmission

  • different innate immunity

flu reassortment

1. coinfection of 2 different viruses in same cell → 8 segments of RNA from each get mixed up

2. RNA reassortment → new virus can have segments from both → hybrid virus

3. hybrid virus can have different antigenic properties

   • different surface proteins = antigenic shift

4. leads to different virus subtype (new HA protein)

5. unrecognised by immune system → pandemic

Antigenic drift

slow gradual change of virus over time

• mutations in glycoproteins (eg HA) over time → change properties

• immune escape → no longer recognised by immune system

• annual vaccines therefore updated

Antigenic shift

Reassortment causes change in HA/antigenic propteries

followed by immune escape

current bird flu outbreak

• H5N1

• spread from poultry into wild birds

• infecting new species, new areas, surviving over summer in uk

• infecting mammals esp sea lions, mink

• millions of poultry culled

• H5 not in humans?