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, H(
• 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. The flu epidemics of history show that antigenic variation of influenza should not be taken lightly, hence the great concern over the recombination of the H5N1 virus in asia through infection of a pig with human and avian strains of flu.

• 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 region, 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

Influenza by Species

Equine Influenza

Subtypes

• Two subtypes of Equine Influenza have been described:
  • H7N7 (Equine 1), which was prevalent in the UK between 1963-1977
  • H3N8 (Equine 2), or the European strains, have been circulating since 1965
• Some drift has occurred, causing outbreaks of North-American-like strains of H3N8 in 1998 (EU) and 2003 (South America)

Pathogenesis

• Aerosol and fomite transmission infects the epithelium of the upper respiratory tract, resulting in cell necrosis
• This manifests a bronchiolitis and serous exudation
• 1-3 day incubation period
• Excretion of the virus in nasal secretions peaks at 3-4 days and finishes by 10 days
• Clinical signs:
  • Harsh dry cough
  • Pyrexia (103-106F)
  • Depression
  • Loss of appetite
  • Enlarged submandibular lymph nodes
• Secondary bacterial infection can follow defective muco-ciliary transport, eg Streptococcus zooepidemicus
• For more, see here

Diagnosis

• Virus isolation: Deep nasal swabs (12 inches) deposited into 10ml of transport medium and transported at 4C
• Antigen detection via ELISA: tests for type A nucleoprotein
• Serology provides a retrospective diagnosis by Haemagglutination Inhibition (HI):
  • Acute and Convalescent (2 weeks post-acute) samples are tested from the same animal
  • 4-fold increase of HI must be shown to confirm diagnosis

Control

• Isolate coughing horses to minimize spread
• Vaccination:
  • All vaccines include H7 and varieties of the current circulating strains of H3
  • Inactivatedegg-grown vaccing is produced with alhydrogel as an adjuvant
  • Live vaccines using purified haemagglutinin do not require adjuvants
  • UK Jockey Club rules regarding timing:
    • Horses must be certified as completing a vaccination course of 3 injections at least 10 days prior to racing
    • The course consists of a primary inoculation followed by a second within 21-92 days and a third after a further 150-215 days
    • Boosters are given annually to maintain immunity, and in the event a year is missed the initial course of three jabs must be repeated

Swine Influenza

Subtypes

• Avian-like H1 and human-like H3 strains vary in virulence

Pathogenesis

• Necrotising bronchiolitis with catarrhal pus
• Barking cough
• Interstitial pneumonia giving consolidation of the lungs and a 'meaty' appearance
• Often associated with bacteria, mycoplasma or immunosuppressive viruses (such as PRRS)
• The virus recycles on farms as litters outgrow maternal antibody at 12 weeks of age
• For more, see here

Diagnosis

• Clinical pneumonia is always suspect
• Serology: retrospective diagnosis by HI

Control

• Isolation of premises
• All-in/all-out systems
• Vaccination is not licensed in the UK

Avian Influenza

Subtypes

• H1-15 and N1-9 have all been isolated
• Highly Pathogenic Avian Influenza (HPAI), caused by H5 and H7 isolates, is also known as Fowl Plague (FP) and is notifiable
  • Chinese poultry are currently the main reservoir for H5N1, not wild birds

Pathogenesis

• HPAI is defined by:
  • Heamorrhages
  • Diarrhoea
  • Sometimes nervous symptoms
  • Sudden death
• H5 spread by feces and infected viscera (kidney/spleen are 100X more infectious than feces)
• H7 and other viruses are carried by 6% of the wild bird population and outbreaks mirror migrating patterns
  • This poses significant risk to free-range flocks

Zoonotic potential

• A 2003 Dutch outbreak of a pathogenic H7 virus caused widespread conjunctivitis and flu-like symptoms with recovery among poultry workers
• Rural chinese children became infected with H5N1 via aerosol transmission, which was limited to upper respiratory symptoms and did not show horizontal spread

Control

• Prevention by proper hygiene and preventing contact with the wild bird population
• Isolation and cull of infected premises
• Firebreak cull in the case of uncontrolled spread
• Vaccination is not currently practiced for the following reasons:
  • An eradication policy prevents it
  • Vaccination favors the evolution of the virus, which might increase its virulence and drift