Just one of many scenarios - Dogs as `mixing vessels' for Influenza
#17,870
Up until 20 years ago, dogs (and cats) were believed largely immune to influenza A infection. All that changed in 2004 when equine H3N8 jumped from horses to greyhounds at a Florida race track (see EID Journal Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida).
Since then canine H3N8 has been sporadically reported across much of the United States and the world. It is considered a `canine specific’ virus, and has not crossed back into horses. Additionally, there have been no reports of human infection.At roughly the same time HPAI H5N1 began infecting big cats in Asian zoos (see Catch As Cats Can).
But 3 years later another, more capable avian virus ( H3N2) jumped to dogs in South Korea (see Transmission of Avian Influenza Virus (H3N2) to Dogs). The HA and NA genes of the A/canine/Korea/01/2007 (H3N2) isolate were closely related to those identified in chickens and doves in South Korea in 2003.
While the canine H3N8 virus has remained fairly stable over the past 20 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 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
In April of 2015, Asian canine H3N2 virus finally arrived in North America (see CDC Statement On H3N2 Canine Influenza In Chicago Region) and quickly spread across the United States.
While quantified as a relatively low-risk virus, in 2017 the CDC added Canine H3N2 to their IRAT (Influenza Risk Assessment Tool) listing of novel flu subtypes/strains 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).
In 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.
Since then we've seen numerous studies on the evolution and zoonotic potential of Canine H3N2, including:
J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2
Emerg. Microbes & Inf.: Genetic & Evolutionary Analysis of Emerging Canine H3N2
Access Microbiology: Inter-Species Transmission of Avian Influenza Virus to Dogs
In the spring of 2023 we looked at a major report published in eLife called Increased Public Health Threat of Avian-origin H3N2 Influenza Virus During Evolution in Dogs, where the authors warned:
We found that, during adaptation in dogs, H3N2 CIVs became able to recognize the human-like SAα2,6-Gal receptor, showed gradually increased hemagglutination (HA) acid stability and replication ability in human airway epithelial cells, and acquired a 100% transmission rate via respiratory droplets in a ferret model. We also found that human populations lack immunity to H3N2 CIVs, and even preexisting immunity derived from the present human seasonal influenza viruses cannot provide protection against H3N2 CIVs.
Those authors have returned with a follow up study (see below) which updates their findings through 2021. They report the emergence of a new clade (5.1) since 2019, and cite additional evidence that CIV H3N2 continues to evolve and adapt.
The link, Abstract, and some excerpts follow, but you'll want to read the report in its entirety. I'll have a bit more after the break.
Surveillance and characterization of avian-origin H3N2 canine influenza viruses in 2021 in China
Published: 11 January 2024 Volume 2, article number 2, (2024)
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Mingyue Chen,Rui Wang, Ying Pei, Ting Zhang, Yanli Lyu, Jonathan McLaughlin, Sai Subramanya Manasa Vemaraju, Zhen Wang, Yipeng Sun & Ming Zhang
Abstract
Avian-origin H3N2 canine influenza virus (CIV) is one of the most prevalent influenza virus subtypes in dogs worldwide. Previous studies have shown that during the evolution of H3N2 CIV in dogs, its adaptability in mammals increased gradually, suggesting that dogs can serve as a potential intermediate host for cross-species transmission of the avian influenza virus.
In this study, we report results from the surveillance and characterization of H3N2 CIVs isolated from animal hospitals and kennels in 2021 in China. We characterized the CIVs’ genetic and antigenic variation, receptor-binding specificity, and virulence in mice. The hemagglutinin (HA) phylogenetic result showed that these H3N2 CIVs belonged to Clade 5.1, a clade formed after 2019.
Compared to the 2016–2019 strains in China, the 2021 H3N2 CIVs had similar antigenicity and receptor-binding specificity. The pathogenicity in mice was significantly reduced after infection with two 2021 strains, but the replication capacity was similar, suggesting that a virus-host balance might have been established. This report emphasizes the importance of close surveillance and monitoring of H3N2 CIVs in dogs to prevent the emergence of novel influenza viruses with public health threats.
(SNIP)
Dogs may play critical roles as mixing vessels and reservoirs contributing to various influenza viruses [13]. Serological and virological data have documented sporadic transmission and subclinical infection in dogs with human influenza viruses [14]. Research also revealed a novel H3N1 virus isolated from infected dogs that resulted from the reassortments of a human-origin H1N1 influenza virus and an avian-origin H3N2 CIV [2]. A novel H3N2 CIV containing the polymerase acidic (PA) segment from the H9N2 avian influenza virus was isolated from a dog in South Korea in 2015 [7].
In addition, canines may serve a role in the adaptation of avian influenza viruses in humans. Our previous studies showed that H3N2 CIV recognized human-like α-2,6-linked sialic acid and acquired a 100% transmission rate via respiratory droplets in a ferret model, suggesting that dogs are potential intermediate hosts for avian influenza viruses to adapt to humans [15]. These studies highlighted the importance of continuous surveillance of H3N2 CIVs in dogs.
For this 2021 study, we focused on animal hospitals and kennels in Beijing and Hainan Province to monitor H3N2 CIV’s circulation. We collected throat swabs from 162 dogs with respiratory symptoms and isolated viral samples to characterize genetic variation, antigenicity, receptor-binding specificity, and replication capability in mammals. To better understand the evolution of the 2021 strains, we compared them with strains isolated in previous years.
Discussion
H3N2 CIV is considered to have originated from avian influenza viruses through adaptive evolution [17]. In the previous study we found that during its adaptation to dogs, H3N2 CIV posed an increased threat to human health. These viruses gained the ability to recognize the human-like SAα2,6-Gal receptor, demonstrated a progressively increased ability to replicate in human airway epithelial cells, and achieved a 100% transmission rate in a ferret model [15]. Therefore, we suggested that dogs are potential intermediate hosts by which some avian influenza viruses have adapted to humans.
In the present study, we monitored H3N2 CIVs in dogs. Seven throat swab samples from 162 dogs with signs of respiratory disease were H3N2 CIV positive. The isolated H3N2 CIVs showed similar genetic and antigenic characteristics, receptor-binding specificity, and replication capability in mice compared to the viruses from 2016 to 2019. However, two strains isolated from 2021 exhibited weakened pathogenicity in mice compared to the 2016–2019 viruses, indicating the establishment of a virus-host balance.
(SNIP)
In summary, our results from this study suggested that the current circulating H3N2 CIVs are evolving to gain a virus-host balance with better replication capability and causing mild symptoms, posing increased public health threats. Our study heightens the importance of close surveillance and monitoring of H3N2 CIVs in dogs to prevent the emergence of novel influenza viruses with the potential to cause public health crises.
While a less pathogenic virus (at least, in mice) may sound like a good thing, it may also be a sign that the virus is becoming better adapted to a murine host. Whether that would carry over into humans remains to be seen.
And of course, it isn't just canine H3N2.
Last May, in China: Emergence of a Novel Reassortant H3N6 Canine Influenza Virus, we looked at a report on the discovery of a new reassorted canine-avian virus circulating in dogs in Liaoning Province over the 2018 to 2019 flu season. The authors reported:
Since the N6 neuraminidase (NA) genes were clustered with the H5N6 AIV, there is a high possibility that these H3N6 CIVs were generated from a H3N2 CIVs and H5N6 AIVs reassortment case.
and
This study indicated that CIVs are evolving and adapting to mammalian hosts at an incredible speed. The H3N2 CIV isolated in November 2018 showed limited replicative ability in vitro and in vivo, but 3 months later, increased replication was detected in March 2019 H3N2 CIV isolates. Moreover, 1 month later, novel reassortant H3N6 CIVs appeared in April 2019. The H3N6 reassortant possessed enhanced mammalian adaption ability compared with H3N2 CIVs.
In addition to H3 viruses, we've also seen avian H6N1 circulating in dogs in Taiwan (see EID Journal: Influenza A(H6N1) In Dogs, Taiwan), serological evidence of H9N2 in dogs in Iran, and the spillover of HPAI H5 viruses in dogs in multiple countries (see J. Virulence: HPAI H5N1 Virus Infection In Companion Animals).
Admittedly, pigs and birds are still better `mixing vessels’ for influenza than dogs or cats, but companion animals are of particular concern because of how closely humans interact with them.
And based on these studies, old `dog' viruses are quite capable of learning new tricks.
