Monday, August 21, 2017

J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2

# 12,706

Up until 2004, dogs were believed largely immune to influenza A infection. All that changed when an equine H3N8 virus mutated enough to adapt to a canine host, and began to spread among greyhounds at a Florida race track 13 years years ago (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida).
A 96% match to the equine H3N8 virus, this canine H3N2 was believed to have jumped directly from horses to dogs without any reassortment.
Since then canine H3N8 has been sporadically reported across much of the United States.  It is considered a `canine specific’ virus, and has not crossed back into horses. Additionally,  there have been no reports of human infection.

About the same time we began seeing reports of dogs infected with avian H5N1; first in Southeast Asia, and then in the Middle East (see Study: Dogs And H5N1). Over time other novel flu viruses would turn up in dogs, including H5N8, H6N1, and pdmH1N1.
More significantly, in 2007 we saw an avian H3N2 virus jump to - and become endemic in - dogs in South Korea  (see Transmission of Avian Influenza Virus (H3N2) to Dogs).
Analysis showed that the HA and NA genes of the A/canine/Korea/01/2007 (H3N2) isolate were closely related to those identified in 2003 from chickens and doves in South Korea.

In April of 2015, this Asian canine H3N2 virus finally turned up in North America (see CDC Statement On H3N2 Canine Influenza In Chicago Region), and since then has spread across much of the United States in a remarkably short period of time.

While the canine H3N8 virus has remained fairly stable over the past dozen years, the same can't be said for the Asian H3N2 virus. We've seen numerous reports coming out of China and Korea suggesting the canine H3N2 may be adapting to other hosts, and continues to reassort with other avian and human flu viruses. Including:
A Canine H3N2 Virus With PA Gene From Avian H9N2 - Korea

Canine H3N2 Reassortant With pH1N1 Matrix Gene

Virology J: Human-like H3N2 Influenza Viruses In Dogs - Guangxi, China

Interspecies Transmission Of Canine H3N2 In The Laboratory

A little over a year ago (May 2016) we saw a study in the Archives of Virology on the Virulence Of A Novel Reassortant Canine H3N2 In Ferret, Dog and Mouse Models which found `significantly enhanced virulence' in mice infected with an H3N2/H1N1pdm reassortant virus.  They wrote:
Thus, we speculate that the natural reassortment between pdm H1N1 and CIV H3N2 can confer virulence and that continuous surveillance is needed to monitor the evolution of CIV in companion animals.
Particularly important because - as companion animals - dogs are often exposed to human flu strains. For that reason dogs are increasingly viewed as potential `mixing vessels’ for influenza reassortment (see Study: Dogs As Potential `Mixing Vessels’ For Influenza).

While quantified as a relatively low-risk virus, last month the CDC added Canine H3N2 to their IRAT (Influenza Risk Assessment Tool) listing of novel flu subtypes/strains that circulate in non-human hosts and are believed to possess some degree of pandemic potential. Their evaluation reads:
H3N2: [A/canine/Illinois/12191/2015]
The H3N2 canine influenza virus is an avian flu virus that adapted to infect dogs. This virus is different from human seasonal H3N2 viruses. Canine influenza A H3N2 virus was first detected in dogs in South Korea in 2007 and has since been reported in China and Thailand. It was first detected in dogs in the United States in April 2015. H3N2 canine influenza has reportedly infected some cats as well as dogs. There have been no reports of human cases.
Summary:  The average summary risk score for the virus to achieve sustained human-to-human transmission was low risk (less than 4). The average summary risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was in the low risk range (less than 4).

All of which brings us to a new study, published online last week in the Journal of Virology, where researchers created and tested canine H3N2 - pdmH1N1 reassortants, and found some `may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs'.

Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus

Hailiang Sun, Sherry Blackmon, Guohua Yang, Kaitlyn Waters, Tao Li, Ratanaporn Tangwangvivat, Yifei Xu, Daniel Shyu, Feng Wen, Jim Cooley, Lucy Senter, Xiaoxu Lin, Richard Jarman, Larry Hanson, Richard Webby and Xiu-Feng Wan*

Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus H3N2 (CIV-H3N2) and equine-origin CIV-H3N8, are enzootic in the canine population. Dogs have demonstrated seroconversion to diverse IAVs and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. 
We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antisera we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting there may be minimal herd immunity in humans.
We assessed the public health risk of CIV-H3N2×pdmH1N1 reassortants by characterizing in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1 identifying some combinations that were more active than either parental virus complex. Using reverse genetics, and fixing the CIV-H3N2 HA, we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued.
Nineteen of these reassortant viruses had high in vitro growth phenotypes and 13 of these replicated in mice lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant efficiently transmitted by contact but not airborne routes and was pathogenic in ferrets.
Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs.

Importance IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained human transmission into a human population with limited herd immunity. The dog, as a potential “mixing vessel” for avian and mammalian IAVs, represents a human health concern due to their susceptibility to infection, large global population and close physical contact with humans.
Our results suggest that humans are likely to have limited preexisting immunity to CIV-H3N2 and that CIV-H3N2×pdmH1N1 reassortants have moderate genetic compatibility and are transmissible by direct contact in ferrets. Our study contributes to the increasing evidence that IAV surveillance in the canine population is an important component of pandemic preparedness.

For more on canine influenza, you wish to revisit:

CDC’s Key Facts On The New H3N2 Canine Flu

JAVMA: Prolonged Viral Shedding Of Canine H3N2

PLoS One: Evidence of Subtype H3N8 Influenza Virus Infection among Pet Dogs in China
Korea: Interspecies Transmission of Canine H3N2

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