Tuesday, November 05, 2019

Vet. Research: Host-range Shift of H3N8 Canine Influenza Virus


Prior to 2002, we've no evidence that influenza viruses circulated in dogs (or cats).  A very few `one-off',  dead-end seasonal flu infections had been reported over the years, but no ongoing transmission. 
That perception began to change in 2003, when dogs and cats were found to be infected with, and many dying from, avian H5N1 in Southeast Asia.
Once again, evidence of ongoing transmission among dogs and cats was lacking (although it may have occurred).  Subsequent laboratory tests (see Avian H5N1 influenza in cats) showed that infected cats shed the H5N1 virus, and could transmit to sentinel cats.

At roughly the same time, an equine H3N8 virus abruptly mutated enough to adapt to a canine host, and rapidly began to spread among greyhounds at a Florida race track in 2004 (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida). 
Two years later, and half-way around the world, another (avian-origin) influenza virus (H3N2) would turn up in domestic dogs in Guangdong Province (see Avian-origin H3N2 canine influenza A viruses in Southern China), and spread rapidly across Asia.
Suddenly, dogs were legitimate hosts for not just one - but two - reassorted novel flu viruses. And these viruses have continued to evolve, spread, and reassort with other viruses, raising concerns that dogs could serve as a `mixing vessel' for influenza (see Study: Dogs As Potential `Mixing Vessels’ For Influenza), much in the way that pigs are viewed today.

These host-range shifts among companion animals have continued; a few years ago we saw evidence that cats were contracting canine influenza (see Korea: Interspecies Transmission of Canine H3N2) from dogs, and dogs were being infected with avian H5N8 (see Korea: Interspecies Transmission of Canine H3N2).
Perhaps most dramatically, in late 2016 we saw an avian H7N2 virus sweep through hundreds of cats housed at multiple New York Animal shelters - while also infecting at least two people- demonstrating that that cats can become efficient transmitters of a novel virus as well.
The exact circumstances that brought about the unexpected species jump of equine H3N8 to dogs, and the ongoing spread of a distinctly canine H3N8 virus, have been a subject of much debate over the years.
We've a fascinating new research report, published this past week in Veterinary Research, that attempts to fill in some of knowledge gaps.  
This is a lengthy, and highly technical paper, and so I've only posted some excerpts.  Follow the link to read it in its entirety.   When you return, I'll have a brief postscript:

Research article
Open Access 

Published: 30 October 2019

Host-range shift of H3N8 canine influenza virus: a phylodynamic analysis of its origin and adaptation from equine to canine host 

Wanting He, Gairu Li, Ruyi Wang, Weifeng Shi, Kemang Li, Shilei Wang,
Alexander Lai & Shuo Su

Veterinary Research volume 50, Article number: 87 (2019)


Prior to the emergence of H3N8 canine influenza virus (CIV) and the latest avian-origin H3N2 CIV, there was no evidence of a circulating canine-specific influenza virus. 

Molecular and epidemiological evidence suggest that H3N8 CIV emerged from H3N8 equine influenza virus (EIV). This host-range shift of EIV from equine to canine hosts and its subsequent establishment as an enzootic CIV is unique because this host-range shift was from one mammalian host to another. 

To further understand this host-range shift, we conducted a comprehensive phylodynamic analysis using all the available whole-genome sequences of H3N8 CIV. 

We found that (1) the emergence of H3N8 CIV from H3N8 EIV occurred in approximately 2002; (2) this interspecies transmission was by a reassortant virus of the circulating Florida-1 clade H3N8 EIV; (3) once in the canine species, H3N8 CIV spread efficiently and remained an enzootic virus; (4) H3N8 CIV evolved and diverged into multiple clades or sublineages, with intra and inter-lineage reassortment. 

Our results provide a framework to understand the molecular basis of host-range shifts of influenza viruses and that dogs are potential “mixing vessels” for the establishment of novel influenza viruses.


Interestingly, current epidemiological data indicate that H3N2 CIV mainly affects pet dogs, while H3N8 CIV affects stray dogs and dogs in shelters. 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 [70] 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.
In conclusion, by conducting a phylodynamic analysis to reconstruct the evolutionary path of CIV, we have not only demonstrated that the interspecies transmission of H3N8 EIV to canine occurred in approximately 2002 but also shown that the progenitor virus was a reassortant virus involving an “ancestral NS1 gene segment”.
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.
Furthermore, H3N8 CIV has diverged into multiple sublineages or clades, possibly as a result of founder effect, in which the founder virus evolves within geographic or facility boundaries. Similar to other influenza viruses, frequent reassortment within and among these clades was observed.
These findings provide a conceptual framework to understand the mechanism of interspecies transmission and host-range shifts of influenza viruses. Finally, although we utilized a computation-intensive genomics approach to reconstruct this host-range shift and the subsequent evolution and adaptation of CIV, phenotypic studies are still required to validate these results. These experiments are ongoing.
       (Continue . . . )

Over the past five years, we've learned a good deal more about the susceptibility of dogs and cats to a variety of avian, swine, equine, and human flu strains. A few recent on-topic blogs include:
PLoS: Adaptation of H3N2 Canine Influenza Virus to Feline Cell Culture
IJID: Animal Influenza Virus Infections in Humans - A Commentary
Emerg. Microbes & Inf.: Characterization of Swine-origin H1N1 Canine Influenza Viruses
Access Microbiology: Inter-Species Transmission of Avian Influenza Virus to Dogs
Arch. Of Virology: Novel Reassortant H5N6 Isolated From Cats - Eastern China
EID Journal: Canine Influenza Virus A(H3N2) Clade with Antigenic Variation, China, 2016–2017

While the next influenza pandemic virus is most likely to emerge from either birds or pigs, companion animals (primarily dogs and cats) have uniquely close relationships with humans, and understanding their role in the evolution and spread of novel flu viruses could prove invaluable.