Friday, April 27, 2018

Emerg. Microbes & Inf.: Genetic & Evolutionary Analysis of Emerging Canine H3N2


Because they live in such close contact with people, companion animals - mostly dogs and cats - are uniquely positioned to serve as a bridge to introduce zoonotic diseases to humans.
This is a topic we've covered previously. For a good summary and CDC webinar, you may wish to revisit  Family Pets, Zoonoses & An Upcoming COCA Call.
Of course, the reverse is also true, as they our pets are constantly exposed to human pathogens (see Companion Animals & Reverse Zoonosis), sometimes with tragic results (see Connecticut: Two Cases Of Fatal H1N1 In Cats).

Although there have always been some pathogens exchanged between dogs (and cats) and humans - up until 14 years ago - influenza wasn't thought to be one of them.

All that changed in 2004 when an equine H3N8 virus mutated enough to adapt to a canine host, and began to spread among greyhounds at a Florida race track (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida).
A 96% match to the equine H3N8 virus, this canine H3N8 was believed to have jumped directly from horses to dogs without any reassortment.
Since then we've seen several more flu viruses turn up in dogs (and cats), including H5N1, H5N8, H1N1, H6N1, and H7N2.

But the most successful canine flu to date has been an avian H3N2 virus, which was first reported in South Korea in 2007(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.
Since then 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
Canine H3N2 arrived in the United States in the spring of 2015 (see CDC Statement On H3N2 Canine Influenza In Chicago Region), and has since  spread across much of the United States in a remarkably short period of time.

While it has never been shown to infect humans, last 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.

Over the past year or so we've looked at several studies suggesting that canine H3N2 continues to show signs of continual evolution and mammalian adaptation.
Emerg. Microbes & Infect.: Virulence, Transmissibility & Evolution of Canine H3N2 Influenza Viruses
J. Infect. Dis.: Molecular, Antigenic & Pathological Features of Canine H3N2 Influenza
J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2

To this growing list we can add another study, published this week in Emerging Microbes and Infections, which takes a deep look at genetic changes in the canine H3N2 virus over time, and by geographic origin.

A few excerpts from a much longer study.  Follow the link to read it in its entirety.
Genetic and evolutionary analysis of emerging H3N2 canine influenza virus
Cheng Zhang1,


The H3N2 canine influenza virus (CIV) originated from an avian species. Since its emergence, it has circulated in multiple states and has caused pandemics among dog populations; however, no comprehensive studies have explored the causes driving these ongoing cases.

The study of the codon usage patterns of viruses can reveal the genetic changes required for the viruses to adapt to new hosts and the external environment. Here we performed a thorough genetic, evolutionary, and codon usage analysis.

We identified three evolutionary H3N2 CIV clades from a timescaled phylogenetic tree, namely, Origin, China, and Korea/USA, by principal component analysis (PCA). Additionally, we found a low codon usage bias and that mutation pressure, natural selection, and dinucleotide abundance shape the codon usage bias of H3N2 CIVs, with natural selection being more crucial than the others.

Moreover, the human codon adaptation index was similar to that of dogs (the natural host) and cats. In addition, the H3N2 CIV similarity index values were higher than those of the avian influenza virus (AIV), suggesting viral adaptation to the host.
Therefore, H3N2 CIVs may pose a potential risk to public health in the future, and further epidemiologic, evolutionary, and pathogenetic studies are required.


Dogs should be carefully considered for their role as influenza hosts because of their close contact with humans and their influenza receptor distribution1, 2.
H3N8 and H3N2 are the current circulating subtypes of canine influenza virus (CIV) in dog populations. H3N8 CIV, which caused a pandemic in dogs, was first isolated in Florida in 20043, and there were no documented reports of CIV infections prior to 20044.
In 2008, Korea first reported H3N2 CIVs, followed by China and Thailand1, 5, 6. In April 2015, the H3N2 CIV circulating in Asia was isolated from an infected golden retriever in Cook County, Illinois. The virus has since spread to several states, causing respiratory disease in thousands of dogs across the United States4.

Of note, a 2012 study showed that a novel H3N1 virus infecting dogs arose by reassortment of a human-origin H1N1 influenza virus and an avian-origin H3N2 CIV. In addition, a 2015 study showed that a novel CIV reassortant, H3N2, containing the polymerase acidic (PA) genomic segment from the H9N2 pandemic avian influenza was isolated from a dog in South Korea.

These developments suggest that dogs may play critical roles as mixing vessels and reservoirs of avian-origin H3N2 CIVs7.
Therefore, canines carrying H3N2 CIV may transmit the virus to other species with whom they have frequent close contact, including humans8. In addition, companion animals may pose a potential public health risk. Although no H3N2 CIV human infections have been reported, the increasing number of new H3N2 CIV cases in the United States and East Asia, as well as the quick evolution of the virus, calls for detailed genetic analysis of emerging H3N2 CIVs to understand and estimate the risk of CIV adapting to humans.

(Continue . . . )

While it may seem a bit of a long shot that the next influenza pandemic will come from companion animals, it was 17 months ago we were monitoring an outbreak of avian H7N2 at several NYC animal shelters, infecting more than 450 cats . . . and one veterinarian.
EID Journal: Characterization Of A Feline Influenza A(H7N2) Virus
For now avian H7N2 and canine H3N2 don't appear ready for prime time, but they - like all influenza viruses - continue to evolve and adapt, and at some point one of them could accrue the right genetic changes to pose a genuine threat.  

For more on the potential companion animals to serve as intermediate hosts for emerging influenza viruses, for canines you may wish to revisit Study: Dogs As Potential `Mixing Vessels’ For Influenza, and for felines Catch As Cats Can