The spread of Equine Flu | Trainer Magazine | European Trainer Article Index

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Sep 28 The spread of Equine Flu

A long look back On November 9th, 1872, almost the entire financial district of the US city of Boston was burnt to ashes. One of the reasons that the Great Boston Fire had such devastating consequences was an epidemic of equine influenza. Horses were so sick that fire wagons had to be pulled by men, and consequently response times were slow. Influenza as a respiratory disease of the horse had been recognised for many years. “After the Great Boston Fire” by James Law, a Scottish veterinary surgeon, reported that diseases “having the general characters of influenza” were known by the Greeks in A.D. 330. But it was not until 1956 that the virus that causes such an important burden on horse populations was isolated in the former Republic of Czechoslovakia and given the not-very-original name of equine influenza virus. Influenza viruses also affect humans and various domestic animals such as pigs, dogs, and birds. However, each species tends to have its “own” virus (i.e. they are speciesspecific) and this is why equine influenza viruses infect horses but not humans and vice versa, although equine influenza has been linked to disease in dogs. Influenza viruses are classified into subtypes, which are defined by the presence of a distinctive set of molecules called Hemagglutinin (abbreviated H, for which 18 different forms exist) and Neuraminidase (abbreviated N, for which there are 11 different forms). The combination of H and N a virus possesses defines its subtype and this is why we often read or hear in the news about H1N1, H7N9, or H5N1 viruses. The equine influenza virus isolated in Czechoslovakia was an H7N7. The emergence of the current flu virus In 1963 there was an outbreak of equine influenza again in the US in Miami, Florida, after the importation of horses from Argentina in South America. To everyone’s surprise, the virus isolated from sick animals was not an H7N7 but an H3N8, something completely different from what was known at the time. A new equine influenza virus had appeared and the rest is familiar to those who have been around horses for a long time: the H7N7 equine influenza virus became extinct (it has not been isolated from horses for almost 40 years) and the H3N8 virus spread to many countries around the world. It has caused devastating pandemics in Australia and South Africa with major loss to the thoroughbred industry in those countries, and H3N8 viruses are still infecting horses today despite the availability of vaccines. A third, killer flu virus What is less well known is that in 1989 there was a large epidemic of influenza in horses in Jilin, China, which was caused by another previously unknown virus, different to the “classical” equine influenza viruses known then. The Jilin virus was highly lethal with mortality reaching up to 20% in some herds. Fortunately, this virus did not spread to other countries and has not been isolated from horses since 1990. Where do “new viruses” come from? The appearance and establishment of a new virus in a given species is known as viral emergence, and the consequences of such events can be devastating, as illustrated Influenza viruses have emerged multiple times in horses, and at least three times in the last 60 years. There is no reason to doubt that they will strike again. Recent scientific advances can help us first to define the antiviral mechanisms and strategies that horses have to fight off viral infections, and second, how certain viruses (but not others) manage to overcome those defenses. If, with the support of the racing industry, we achieve these goals, then we will be closer to predicting, controlling, and perhaps even preventing the devastating consequences of future influenza viruses emerging in horses. WORDS: PablO R. MuRcia, JOhn F. MaRShall PhOTOS: PROFESSOR cElia MaRR The map highlights the countries where new equine influenza viruses emerged since 1956 by the 2009 human influenza pandemic. If we ask ourselves where new influenza viruses come from, the answer is very simple: they come from other animals. The human influenza virus that caused the 2009 pandemic came from pigs, while the three different equine influenza viruses that we described above are thought to have originated in birds. Wild aquatic birds possess the highest diversity and abundance of influenza viruses in nature and therefore they are thought to be the source of viruses of other species. Will novel flu viruses continue to emerge? An important question for those of us interested in improving the health of horses is whether new influenza viruses could emerge in horses in the future. While the most likely answer is yes, it is really difficult to determine when and where it will happen and what the consequences will be. starting to find out. Flu viruses live and multiply within the cells of their host. To do this they have to be able enter their target cells and use the cellular machinery they find there to replicate. This is not an easy task, because it requires highly coordinated interactions between viral and cellular proteins (i.e. the molecules that carry out viral replication) and second, because horses are equipped with very effective natural antiviral defense mechanisms. For example, the mucus present in the respiratory tract helps prevent viral infections. The obstacles that viruses have to surmount in order to infect and establish in new hosts are known as the species barrier. The species barrier is very effective, as illustrated by the fact that horses are exposed to numerous influenza viruses of humans and other animals without getting infected. Just think how often horses are in direct or indirect contact with birds, dogs, or pigs. “Wild aquatic birds possess the highest diversity and abundance of influenza viruses in nature and are thought to be the source of viruses of other species ” ISSUE 55 TRAINERMAGAZINE.COM 43 Being able to predict which viruses will emerge in horses would be invaluable because it will allow us to take actions to prepare for those events and perhaps even prevent them. Such predictive knowledge requires a deep understanding of the mechanisms that allow influenza viruses to infect and become transmissible among horses, and this is something we are jus Can science protect horses from future fl u pandemics? The horse genome was sequenced in 2009. Viruses also encode their genetic material, either as DNA like mammals or RNA, a similar molecule. Specifi c genomes of many equine infl uenza viruses have been mapped going back to those isolated in 1956. In fact almost 600,000 infl uenza virus sequences are available and over 5,500 of these are equine infl uenza virus sequences. Why is that helpful? Sequencing technology enables us to identify genes that horses have to protect themselves against viral infections and to work out which genes are turned on and off in a cell or tissue when the horse meets a foreign invader like a virus. We can identify the equine genes that are turned on by the virus in order to replicate and also work out which equine antiviral genes the virus must switch off in order to take up residence in the horse. Fortunately, this sort of scientifi c experiment can be achieved by looking at cells in the laboratory and does require live animals to be infected with fl u for experimental purposes. But if VETERINARY 44 TRAINERMAGAZINE.COM ISSUE 55 “The genomes of infl uenza viruses are constantly changing as they acquire mutations in every infection. Some of these mutations will harm the virus but others are benefi cial we want to know how viruses manage to ” infect horses, looking at genetic changes in infected horse cells is only half of the story. The other half is likely to be found in the genome of the virus. The genomes of infl uenza viruses are constantly changing as they acquire mutations in every infection. Some of these mutations will harm the virus but others are benefi cial; for example, a mutation can allow the virus to escape vaccine immunity and it is for this reason that infl uenza vaccines need to be regularly updated. Mutations can also allow the virus to infect a new host species. There are literally hundreds of thousands of infl uenza genomes available in public databases. By using computer science tools, we can identify those mutations that differentiate avian from equine infl uenza viruses. The effect of individual mutations on the ability of a virus to infect or adapt to a new species can then be tested under experimental conditions. But this information will have direct practical benefi t as it will allow us to determine how much of a risk a given virus poses to horses. However, we are still far from being able to make such predictions, and research to fi ll this knowledge gap is currently just beginning How is the racing industry supporting fl u research? Signifi cant support for the investigation of equine infl uenza has come from the horseracing industry through the Horserace Betting Levy Board (HBLB). One of the research centres currently supported by the HBLB is the Centre for Virus Research (CVR) of the University of Glasgow. The CVR carries out multidisciplinary research on viruses and viral diseases of humans and animals for the improvement of human and animal health. Researchers at the CVR apply a broad range of expertise to the study of equine infl uenza, from epidemiology, mathematical modelling, and bioinformatics to viral ecology, molecular, and structural virology. Through a range of HBLB research and educational funding streams, researchers at the CVR are investigating how the horse responds to infection and how infl uenza has adapted to the horse in order to overcome this immune response. This knowledge will, in turn, help us overcome the threat to our horses from the fl u virus. Horses, like other animals, possess effective mechanisms that protect them against viral infections from other animals in nature. These mechanisms constitute the species barrier A cell infected with equine infl uenza virus (shown in red) observed under a fl uorescent microscope. Molecular biology studies are essential to understand how viruses overcome the barriers to infection

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This article appeared in - European Trainer, Issue 55, October to December 2016

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