Wednesday, June 06, 2018

mBio: Novel Reassortant Influenza A Viruses in Canines in Southern China


While we tend to focus primarily on the pandemic potential of avian and swine flu viruses, these are not the only hosts capable of serving as `mixing vessels' for influenza A. Over the years we've looked at novel flu in a number of species, including in bats, camels, harbor seals, mink, and many other small mammals
But because they live in such close contact with humans, dogs and cats are viewed as being in a unique position to introduce zoonotic diseases to humans.
And increasingly over the past decade, we've seen they are susceptible to a wide variety of influenza A viruses, including those of avian, human, and swine origin (see Study: Dogs As Potential `Mixing Vessels’ For Influenza and for felines Catch As Cats Can)

While canine H3N2 and H3N8 are the most obvious concerns for zoonotic transmission from canines (see CDC IRAT on Canine H3N2), over the past few years we've also seen a number of more `exotic' infections including:
Avian H7N2 Virus in Human Exposed to Sick Cats

Human-like H3N2 Influenza Viruses In Dogs - Guangxi, China

Canine H3N2 Reassortant With pH1N1 Matrix Gene

Korean CDC Statement On H5N6 In Cats

Influenza A(H6N1) In Dogs, Taiwan

Yesterday the journal mBio published a study that reveals there is an even greater variety of canine infection with novel flu viruses in Southern China than was previously known. 

First the abstract and link, then I'll return with more.
Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China
Ying Chena,b,c, Nídia S. Trovãob,c,d, Guojun Wangb,c, Weifeng Zhaoa, Ping Hea, Huabo Zhoua,e, Yanning Moa, Zuzhang Weia, Kang Ouyanga, Weijian Huanga, Adolfo García-Sastreb,c,f, Martha I. Nelsond


The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans.
Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans.
First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1.
Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]).
CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve.

IMPORTANCE Mammals have emerged as critically under recognized sources of influenza virus diversity, including pigs that were the source of the 2009 pandemic and bats and bovines that harbor highly divergent viral lineages.
Here, we identify two reassortant IAVs that recently host switched from swine to canines in southern China, including one virus with known zoonotic potential. Three additional genotypes were generated via reassortment events in canine hosts, demonstrating the capacity of dogs to serve as “mixing vessels.”
The continued expansion of IAV diversity in canines with high human contact rates requires enhanced surveillance and ongoing evaluation of emerging pandemic threats.

The full open access study (which is very much worth reading in its entirety) can be accessed here.
The ecology of canine flu viruses is far different in China than in most other countries because while dogs are often treated as pets, they are also still raised as a food source in some regions, giving them greater exposure to other species such as swine and poultry (see China: Avian-Origin Canine H3N2 Prevalence In Farmed Dogs).
Notably, one of the two swine-origin viruses discovered circulating in dogs in this study (CIV-H1N1(sw2)) is of the same genotype as the EAH1N1 virus which as been cited as one of the biggest pandemic threats in China (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza).

A little less than two years ago we looked at the zoonotic transmission of this emerging novel swine virus in EID Journal: Reassortant EAH1N1 Virus Infection In A Child - Hunan China, 2016, an incident which is referenced below in the discussion section.


This study demonstrates the capacity of canines in southern China to serve as reservoirs for the evolution of novel reassortant IAVs. Importantly, we identified two viruses of swine origin that were introduced into canines in Guangxi, China: CIV-H1N1(sw1) and CIV-H1N1(sw2). CIV-H1N1(sw1) viruses were more frequently identified in canines, with evidence of onward transmission across multiple years and prefectures and providing opportunities for multiple genomic reassortment events with the CIV-H3N2 lineage already established in Asian canines. Three new reassortant IAV genotypes were generated: CIV-H1N1r, CIV-H3N2r, and CIV-H1N2r

Alarmingly, a virus with the same genotype as CIV-H1N1(sw2) viruses was recently isolated from a human [A/Hunan/42443/2015(H1N1)] (36), representing a likely case of swine-to-human transmission and demonstrating the zoonotic potential of viruses identified in canines with the same genotype. 

Further surveillance is greatly needed to determine which of the five genotypes continue to transmit in dogs in Guangxi, whether the viruses have disseminated to other regions of China, and whether additional reassortant genotypes have been generated. 
        (Continue . . . )

Since the influenza subtypes that commonly circulate in swine (H1, H2 & H3) are also the same that have caused all of the human pandemics going back 130 years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), they are generally regarded as having less far to `jump’ to humans than many avian viruses.
Which is precisely how the H1N1 pandemic virus emerged in 2009, after kicking around (and reassorting in) swine herds for a decade or longer.
Which is why we take studies like today's seriously.  While there are many possible zoonotic routes the next pandemic could take, the growing body of evidence suggests that swine-to-canine-to-human is not as much of a long shot as was once believed.