Orthomyxoviridae

BACK TO VIRUSES

Introduction

Influenza is a largely species-specific infection, but the threat of zoonotic potential is real. Virulence varies between strains, but all are spread by aerosol routes. They are typified by rhinitis, pyrexia, and anemia. Flu presents a particular challenge to vaccination as antigenic drift within the virus means that strains can vary from one year to the next. As such, vaccine produced from this year's virus may not give protection against next year's virus.

Morphology

• Enveloped, single-stranded RNA negative sense virus with a different gene on each of its 8 segments
• Each gene codes for one protein:
  • Haemagglutinin (H) spike
  • Neuraminidase (N) spike
  • Matrix, which lines the envelope and acts as scaffolding
  • Nucleic acid
  • 3 viral polymerases
  • 1 large non-structural protein
• Each strain of flu is named according to it's H and N number, eg. H5N1
  • Haemagglutinin binds virus to respiratory epithelia via sialic acid
  • Neuraminidase is a sialidase enzyme that prevents reattachment to the same host cell upon detachment

Virulence

Virulence depends on the tropism of the H molecule involved:

• H is formed by the cleavage of a precursor protein H0
• Cleavage typically happens in respiratory or enteric epithelia
• However, a virulent virus has more basic amino acids at it's H0 cleavage site, leaving it open for cleavage by other cells, such as neurons

Types and Subtypes

• Three genuses of Flu exist: A, B, and C, of which only A is of veterinary interest
• The subtype of a flu virus is described in terms of H (of H1-H15) and N (of N1 to N9)
• Subtype by species:
  • Ducks: H1-H15
  • Equine: H7 (previously Equine type 1) and H3 (previously Equine type 2)
  • Harp seals: H4 and H7
  • Pigs: H1, H3, H4, H5 (Asian), H9
  • Human: H1-3, H7, H9
• Vaccines cannot cross protect against different subtypes within the same species

Antigenic Shift and Drift

• Flu continues to be a feared disease because of it's ability to evolve, both within a particular strain and into new and undefined strains
• Shift is the more serious of antigenic movements and is definied by:
  • Gene reassortment
  • Change of species specificity
• Drift is the evolution of a virus within its subtype, evidenced by the changing strains of human flu from year to year
  • Each H spike carries 4 antigenic regions, and a change in any region results in drift
  • Viral RNA is constantly evolving to evade immune detection and destruction
• Vaccination schemes are affected by both shift and drift:
  • Complete change of H spike renders current vaccinations useless, and is the cause of an epidemic
  • Current vaccines are always modeled on the most recent outbreaks of the flu in question, and cannot therefore protect against the evolution of the virus from year to year
  • Partial protection can be provided against strains within the same subtype, hence the continuation of vaccination shemes