Flu’s journey from horses to dogs: It all began in Florida

The influenza virus viewed under an electron microscope. Image: Centers for Disease Control and Prevention
Influenza virus viewed under an electron microscope. Image: Centers for Disease Control and Prevention

Scientists have delved into one of the Influenza A virus’s most troubling party tricks — making a successful jump from horses to dogs.

Before 2003, there was no evidence of a dog-specific influenza virus, despite the species’ close contact with humans and with other mammalian species, such as swine and equines, which are prone to flu viruses.

There had been serological evidence found of influenza A virus in dogs, but these were “dead-end” infections, as there was no further sustained spread among dogs.

That all changed about 17 years ago. Influenza A virus became established in dogs.

Researchers from Nanjing Agricultural University in China set out to learn more about the host shift from horses which gave rise to the now well-established H3N8 canine influenza virus.

Wanting He and his colleagues, writing in the journal Veterinary Research, said molecular and epidemiological evidence suggests that the H3N8 canine influenza virus emerged from the H3N8 equine influenza virus.

This host-range shift from equine to canine hosts and its subsequent establishment in dogs is unique, they say, because it occurred from one mammalian host to another.

The study team conducted a comprehensive analysis using all the available whole-genome sequences of the H3N8 canine flu virus — 44 in all.

They found that its emergence occurred between 2002 and 2003.

This interspecies transmission was by a reassortant virus of the circulating Florida-1 clade H3N8 equine flu virus. Reassortment is the process by which influenza viruses swap gene segments.

Once in dogs, the H3N8 canine variant spread efficiently and continues to circulate among dogs. It is continuing to expand in its geographic distribution and canine host breeds.

The canine form has since evolved and diverged into multiple clades or sublineages, with intra and inter-lineage reassortment.

Interestingly, the evidence points to this jump occurring in Florida — the same US state in which the H3N8 equine flu virus was first identified in Florida in 1963.

The H3N8 equine flu virus has since diverged into American and Eurasian lineages, and subsequently, the American lineage further diverged into multiple clades, including Florida-1, from which the H3N8 canine flu virus is derived.

Curiously, there is evidence of an H3N8 equine flu virus infection in British foxhounds around 2002. This was closely related to representatives of a sub-lineage of American viruses, but without viral isolation, it is difficult to know if the virus infecting the British foxhounds was the same as that from Florida.

However, this virus did not kick on to become established in dogs.

“Why did these two events of interspecies transmission by an apparently similar contemporary equine influenza virus result in different clinical outcomes?” the researchers asked.

“Our results indicated that the emerging H3N8 canine influenza virus was a reassortant virus that had fully adapted to the canine host when it emerged in 2002.

“However, whether there were multiple ‘attempts’ by H3N8 equine influenza virus to establish in a canine host or whether there were ‘back-n-forth’ progenitor viruses between the two host species, of which one successfully established, remains a major knowledge gap.”

The study team said interspecies transmission of influenza viruses might occur more frequently than previously thought.

“But to adapt and remain in a new host species, that is, to undergo a host-range shift, unique combinations of gene segments plus critical mutations are required.”

They continued: “Given the recent report of the susceptibility of dogs to a wide spectrum of influenza viruses, the high frequency of reassortment among these influenza viruses and that stray dogs have a high risk of contact with other species, including birds and humans, the risk of dogs as a ‘mixing vessel’ generating a pandemic influenza virus should not be overlooked.”

The full team comprised Wanting He, Gairu Li, Ruyi Wang, Kemang Li, Shilei Wang and Shuo Su, all from Nanjing Agricultural University; Weifeng Shi from Taishan Medical College; and Alexander Lai, from Kentucky State University.

He, W., Li, G., Wang, R. et al. Host-range shift of H3N8 canine influenza virus: a phylodynamic analysis of its origin and adaptation from equine to canine host. Vet Res 50, 87 (2019) doi:10.1186/s13567-019-0707-2

The study, published under a Creative Commons License, can be read here


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