When it comes to zoonotic influenza – all the various flu viruses out there which originated in animal populations before jumping into humans – there are two big hitters: bird flu and swine flu. But with the publication of a new study out of China, scientists are warning that we may soon see the rise of another type of zoonotic flu – and this one might be coming to us via man’s best friend itself.
Researchers "systematically investigated the evolution of genetic and biological properties of [an] avian-origin virus during its circulation in dogs,” reads the paper, published this month. “We found that during the adaptation of H3N2 CIVs to dogs, H3N2 CIVs became able to recognize the human-like SAα2,6Gal receptor, showed gradually increased HA acid stability and replication ability in human airway epithelial cells, and had a 100 percent transmission rate via respiratory droplets in a ferret [model].”
Or to put it in other, more worrying words: “Our results revealed that dogs might serve as potential intermediate hosts for animal influenza viruses’ adaption to humans.”
What is “dog flu”?
Like so many of those zoonotic influenza viruses that infect humans, the illness now thought of as “dog flu” was originally a version of bird flu – H3N2, to be precise. It wasn’t known to infect dogs until around 2006 – but in the years since then, it has firmly established itself in canines, evolving into a fully-fledged mammalian form of avian influenza.
“The virus does not seem to pose particularly worrying health threats to dogs,” James Wood, head of the department of veterinary medicine at the University of Cambridge, told The Telegraph – though he agreed that it’s “pretty clear” that the flu strain is now a dog-specific virus.
It’s a situation that has long worried experts. While avian flu strains can cause severe illnesses in humans, their spread is usually limited past the initial infected patient – the type of receptor molecule the virus is best equipped to infect simply doesn’t exist at high enough concentrations in human upper respiratory tracts, making it difficult for the virus to spread from person to person.
But a strain of bird flu mutating in a way that could help it survive and transmit between mammals – even species as unlike ourselves as dogs – would presumably be much better equipped to infect humans at a large scale. To put it bluntly: if this strain of flu really can infect humans, your beloved family pet may become patient zero for a pandemic.
“The changes in the canine virus apparently are making it better adapted to transmit within mammals, as you might expect after such a long period in dogs,” Wood told The Telegraph. “One might be more concerned about the longer term pandemic potential.”
How was the study conducted?
So, what’s the evidence for such a dramatic statement? It comes as the result of a huge analysis of more than 4,000 nasopharyngeal swabs from wheezy dogs across two years and nine provinces or municipalities of China.
Of those sick dogs, only around one in 20 tested positive for H3N2 – though the researchers noted that the incidences increased dramatically over the study period. More important than the raw numbers of infections, however, was what the team found when they sequenced the genome of the virus strain: “compared with ancestral avian influenza viruses,” they confirm in the paper, “H3N2 [viruses] that were initially introduced to dogs possessed several substitutions identical to human influenza viruses with high frequencies.”
The rate of those adaptations, they point out, seems to have sped up recently – with a big hike in human-friendly mutations turning up after 2016. “These results indicated that H3N2 [viruses] may have increased their adaptability to humans during their evolution in dogs,” the team concludes.
That may be a problem – since, as the researchers also discovered, human immune systems don’t appear to have any natural protection against the virus. “No H3N2 [virus] was recognized by antisera to H3N2 human seasonal influenza virus in […] assays,” they write.
“These results indicated that human populations lack immunity to [the] H3N2 [canine influenza virus],” they confirm, “and even pre-existing immunity derived from the present human seasonal influenza viruses cannot provide protection against H3N2.”
Combined with a second approach in which the team deliberately infected small groups of dogs and ferrets with the H3N2 canine and avian influenza viruses – with the result that certain clades spread very effectively among both mammalian species – and the data certainly “warrants attention,” Ian Jones, a professor of virology at the University of Reading, told The Telegraph.
“It’s a data-rich paper that surely shows that the most recent viruses […] are more adapted to mammals than was the original virus that made the leap from an avian,” he said.
Of course, there’s no evidence of dog flu having infected humans as yet – but with the high number of mutations, Jones agreed, the study provides evidence that the virus is “creeping” towards being human-like.
Should we be worried?
Let’s face it: there’s nothing like talk of new pandemics to which humans have no existing immunity for getting people riled up. But how seriously should we be taking this possibility?
According to Jones, we shouldn’t be overreacting just yet. “At the moment I judge this data warrants attention,” he told The Telegraph, but "the case for a ‘threat’ is not clear.”
Despite the researchers’ contention that humans have no pre-existing immunity to the virus, Jones suggested the situation may not be as dire as it first seems. Even if human immune systems have no protection against infection, he said, there may yet be some protection against the disease itself.
While the increasing and accelerating number of mutations in the viral genome may seem concerning, he argued, “some of this is just the virus settling down in the dog, so inevitably becoming mammalian virus-like.”
Meanwhile, it bears repeating that there has been no evidence so far of any human cases of dog flu. That fact may paradoxically make those high numbers of human-infecting mutations a cause for optimism, Wood suggested: perhaps, he told The Telegraph, it implies the potential for human infection isn’t that high after all.
Of course, it’s not a guarantee – perhaps the canine influenza virus simply hasn’t reached the mutation threshold that would allow it to effectively infect humans. And should the virus spill over into humans, it could be virtually impossible to contain, Jones cautioned.
“In some countries dog control would be impossible and in others socially difficult,” he said. “I think the obvious thing is surveillance and an awareness in influenza reference centres of the dog adapted sequences so any human cases can be reported quickly.”
The study is published in the journal eLife.
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