Tuesday, September 26, 2017

J. Infect. Dis.: Molecular, Antigenic & Pathological Features of Canine H3N2 Influenza


While avian, swine, and human influenza viruses tend to get the bulk of our attention, there are other host-adapted influenza viruses that are viewed as having at least some zoonotic potential.  Some of the more obscure flu viruses we've looked at in the past include:
That Touch Of Mink Flu (H9N2) - Revisited
Sci Rpts: Avian & Human Influenza Compatible Receptor Cells In Little Brown Bats
Serological Evidence Of Influenza D Among Persons With & Without Cattle Exposure
mBio: A Mammalian Adapted H3N8 In Seals
Report: Skunks and Rabbits Can Catch And Shed Avian Flu

Human contact with seals, bats, skunks, and even mink are fairly limited - at least compared to contact with birds, swine, and members our own species - and that likely lowers the risk of these viruses jumping successfully to humans.
But there is one other category to which many of us do have close, prolonged contact; companion animals (primarily dogs & cats).
Until early in the last decade, both dogs and cats were thought to be relatively immune to influenza A viruses. All that changed when an equine H3N8 virus mutated enough to jump to a canine host (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida).
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 and cats 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.

This avian-origin canine H3N2 first spread into China, finally arriving in the United States in the spring of 2015, where it has since spread across the country. Again, as with canine H3N8, no human infections have been reported. 

What we have seen are numerous reports coming out of China and Korea suggesting the canine H3N2 may be adapting to other hosts, and that it 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 looked at 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.
And just over a month ago we looked at another study (see J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2) where researchers created and tested canine H3N2 - pdmH1N1 reassortants, and concluded some `may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs'
Both worth noting 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).
All of which brings us to a new study, published this week in the Journal of Infectious Diseases, which looks at the potential for canine H3N2 to reassort with human (or other) flu strains, and pose a threat to public health.

While the full article is behind a paywall, we can get the gist from the abstract below.

Assessment of Molecular, Antigenic, and Pathological Features of Canine Influenza A(H3N2) Viruses That Emerged in the United States

Joanna A Pulit-Penaloza Natosha Simpson Hua Yang Hannah M Creager Joyce Jones Paul Carney Jessica A Belser Genyan Yang Jessie Chang Hui Zeng

The Journal of Infectious Diseases, Volume 216, Issue suppl_4, 15 September 2017, Pages S499–S507, https://doi.org/10.1093/infdis/jiw620

19 September 2017


A single subtype of canine influenza virus (CIV), A(H3N8), was circulating in the United States until a new subtype, A(H3N2), was detected in Illinois in spring 2015. Since then, this CIV has caused thousands of infections in dogs in multiple states.


In this study, genetic and antigenic properties of the new CIV were evaluated. In addition, structural and glycan array binding features of the recombinant hemagglutinin were determined. Replication kinetics in human airway cells and pathogenesis and transmissibility in animal models were also assessed.


A(H3N2) CIVs maintained molecular and antigenic features related to low pathogenicity avian influenza A(H3N2) viruses and were distinct from A(H3N8) CIVs. The structural and glycan array binding profile confirmed these findings and revealed avian-like receptor-binding specificity. While replication kinetics in human airway epithelial cells was on par with that of seasonal influenza viruses, mild-to-moderate disease was observed in infected mice and ferrets, and the virus was inefficiently transmitted among cohoused ferrets.


Further adaptation is needed for A(H3N2) CIVs to present a likely threat to humans. However, the potential for coinfection of dogs and possible reassortment of human and other animal influenza A viruses presents an ongoing risk to public health.

While currently quantified as a relatively low-risk virus, over the summer 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).

 For more on the evolution of 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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