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Influenza virus continually evolving

by
01 March 2010, at 12:00am

OLIVER DAVIS provides an overview of equine influenza

AN awful lot is being said about influenza these days. We’re bombarded with reports on “pig flu”, “bird flu”, H1N1 pandemics – over a period of time it’s easy to lose the forest for the trees. How can we summarise influenza and how it relates to us, and particularly the horse?

Influenza viruses are classified into types A, B, and C which can be traced back phylogenetically to a single avian virus which diverged approximately 8,000 years ago to create the C virus gene. A further split occurred again 4,000 years later to form the respective A and B virus gene we recognise today.1 

Influenza A viruses cause all clinically significant influenza diseases in mammals and birds, including epidemics and pandemics. Influenza B and C viruses are mainly isolated from humans and are less pathogenic than Influenza A viruses.

Influenza viruses belong to the family of Orthomyxoviridae and have a segmented, single-stranded RNA genome which is imbedded in the nuclear matrix. Two types of glycoproteins protrude out of the nucleoprotein and through the surrounding envelope – the Hemagglutinin (HA) and Neuraminidase (N).

HA is vital to the binding and entry into the host cell. NA plays a fundamental role in the release of freshly budding virions from the cell. The glycoproteins are also key stimulators of the body’s immune response and therefore confer the influenza virus with its specific antigenic properties.

A systematic code is employed to describe influenza viruses. This includes the virus type (A, B or C), followed by the animal species, place the virus was discovered, isolate number, isolation year, followed in parentheses by the H and N subtypes. For example, the first virus isolated from horses was found in Prague in 1956: A/equi/Prague/1/56(H7N7).

Aquatic birds remain the natural reservoir for influenza A viruses and serve as a springboard for infecting the various species that come into contact with them. 

Although we tend to think of influenza as an infectious disease that only affects humans, horses, pigs and birds, it is becoming increasingly evident that this assumption is incorrect.

Interspecies transmission of EI from horses to dogs by an H3N8 virus has been reported on several occasions, including a widely reported outbreak in 2004 in which eight out of 24 racing greyhounds died from haemorrhagic pneumonia following infection from contagious equine influenza.2 Furthermore, it has been shown that H3N8 infection can be transmitted to other dog populations.3

Infection concern

In Asia, respiratory disease in dogs has been reported following infection with H3N2 and the highly pathogenic avian influenza virus H5N1. N5N1 has also been shown to infect large felids4,5 and domestic cats6, a fact that has caused concern recently for both veterinary and public health. Reassuringly, there have been no reports to date of humans contracting the infection from diseased dogs or cats.

What makes the influenza virus so resilient is the ability to change its antigenic profile over a period of time. It is able to do this through the use of antigenic shift and drift. A closer look at the make-up of the influenza virus will help understand these properties better.

As all viruses, the influenza virus in effect “borrows” the host cell’s own genetic reproducing capabilities. However, since the virus’s RNA polymerase does not have a double- checking mechanism, random point mutations occur relatively frequently. This antigenic drift helps to evade the host’s immune response. Another characteristic feature of the RNA genome is that it is segmented. This is important when two or more different influenza virus strains invade the same host cell: similar to predisposing tear lines in continuous feed computer paper, the segmented areas can swap with other influenza virus strains to form a new subtype which consists of a mixture of surface glycoproteins from the original strains.

Not only have the features of antigenic shift and drift allowed for the influenza virus to continually evolve, unfortunately natural infection confers only a very limited immunity of short-term duration. Regular widespread vaccination with relevant strains remains the only suitable method to protect against infection.

Different rate

Interestingly, the rate of antigenic change is not the same for each species. In horses, for instance, the natural evolution of the influenza virus is slower than in humans. Since being isolated in 1956, two major subtypes have evolved for equine influenza: Subtype 1 (A/Equi- 1H7N7) which is no longer in circulation worldwide and Subtype 2 (A/Equi-2 H3N8) which has split into two lineages, a “European” lineage and an “American” lineage. Currently, it is the “American” lineage that is actively evolving and causing EI outbreaks throughout the world.

The most recent major epidemic occurred in 2007 when EI struck Australia7 and spread swiftly throughout the naïve population, affecting over 47,000 horses8 and virtually bringing the equine industry to its knees. In response to this, the OIE has recommended that manufacturers update the strains to ensure protection against a Sydney ’07 viral type strain.9,10,11

There are currently four influenza vaccines in the UK that are licensed for use in horses. All of these have proven efficacy against equine influenza. Although not all have yet managed to update their strains, most manufacturers have conducted clinical trials to demonstrate that their vaccine can cross-protect against the Sydney ’07 strain.

However, as the manufacturers do implement the update, don’t expect to see Sydney ’07 in the list of employed strains. What you will find is an American lineage strain that is closely related to the virus that was isolated in South Africa in 2003. This appears to be more virulent and immunogenic than the strains recovered from the most recent outbreaks.

A differing feature between the licensed vaccines is the technology employed to induce an immune response. Not only are there differences in the adjuvant, the immune-enhancing medium which carries the viral suspension, but pharmaceutical companies have chosen different technologies to manufacture their vaccine.

These range from a relatively simple whole virus technology which uses the entire killed virus, to sub-unit technology which only includes the major antigen stimulating components (HA and/or N) of the virus. There is also a genetically modified equine influenza vaccine available which employs a canary pox virus as a vector.

Although the vaccines will all have similar qualities, careful scrutiny of the data sheet is advisable.

References

  1. Yoshiyuki, S. and Masatoshi, N. (2002) Origin and Evolution of Influenza Virus Hemagglutinin Genes. Mol. Biol. Evol. 19: 501- 509.
  2. Crawford, P., Dubovi, Castleman, Stephenson, Gibbs, W., Chen, L., Smith, C., Hill, R., Ferro, P., Pompey, J., Bright, R. and Medina, M., Influenza Genomics Group, Johnson, C., Olsen, C., Cox, N., Klimov, A., Katz, J. and Donis, R. (2005) Transmission of Equine Influenza Virus to Dogs. Science 310: 482-485
  3. Yamanaka, T., Nemoto, M.,Tsujimura, K., Kondo, T. and Matsumura, T. (2009) Interspecies transmission of equine influenza virus (H3N8) to dogs by close contact with experimentally infected horses. Veterinary Microbiology 139 (3-4): 351-355. 
  4. Keawcharoen, J., Oraveerakul, K., Kuiken, T., Fouchier, R.A., Amonsin, A., Payungporn, S., Noppornpanth, S., Wattanodorn, S., Theambooniers, A., Tantilertcharoen, R., Pattanarangsan, R., Arya, N., Ratanakorn, P., Osterhaus, D.M. and Poovorawan, Y. (2004) Avian influenza H5N1 in tigers and leopards. Emerg. Infect. Dis. 10: 2,189-2,191.
  5. Amonsin, A., Payungporn, S., Theamboonlers, A., Thanawongnuwech, R., Suradhat, S., Pariyothorn, N.,Tantilertcharoen, R., Damrongwantanapokin, S., Buranathai, C., Chaisingh, A., Songserm, T. and Poovorawan, Y. (2006) Genetic characterization of H5N1 influenza A viruses isolated from zoo tigers in Thailand, Virology 344 (2): 480-491.
  6. Kuiken, T., Rimmelzwaan, G.F., Van Riel, D., van Amerongen, G., Baars, M., Fouchier, R. and Osterhaus, A. (2004) Avian H5N1 influenza in cats. Science 306: 241.
  7. Cowled, B., Ward, M., Hamilton, S. and Garner, G. (2009) The equine influenza epidemic in Australia: Spatial and temporal descriptive analyses of a large propagating epidemic. Preventive Veterinary Medicine 92 (1-2): 60-70.
  8. 8. www.dpi.nsw.gov.au/agriculture... horses/health/general/influenza/summary-of- the-200708-ei-outbreak.
  9. Bryant, N., Paillot, R., Rash, A., Medcalf, E., Montesso, F., Ross, J., Watson, J., Jeggo, M., Lewis, N., Newton, J. and Elton, D. (2010) Comparison of two modern vaccines and previous influenza infection against challenge with an equine influenza virus from the Australian 2007 outbreak. Vet. Res. 41: 19
  10. AHT trial (2009) EQ-230-2008. 11. Intervet Subject Report EQC 06-12-036A.