Dogs May Offer Missing Link in Coronavirus Evolution

How did the novel coronavirus jump from animal to human? Stray dogs roaming a so-called wet market may have helped.

(CN) — Like a stamp in a passport, every host leaves an imprint on a virus’ genetic code, offering clues to its evolutionary pathway. Research published Tuesday in the journal of Molecular Biology and Evolution makes the case that dogs could have been an intermediary host for the novel coronavirus SARS-CoV-2.

Most researchers pinpoint the Wuhan province of China as the place where the novel coronavirus first infected humans. Since December, the virus has spread to nearly 2 million people worldwide, causing them to suffer the adverse effects of Covid-19. Researchers continue to report evidence of similar betacoronaviruses in bats and pangolins — animals sold in unregulated wet markets — that may have leapt to humans.

Still, none of the viruses presented thus far provide a perfectly clear evolutionary pathway.

“The intermediate species is always difficult to identify because it is typically not sickened by the viral infection,” explained Dr. Xuhua Xia, the paper’s author and a biology professor at the University of Ottawa in Canada.

Researchers around the world have homed in on three key genomic signatures in SARS-CoV-2, including “a 12-nt insertion leading to a polybasic furin cleavage site” that is absent from the betacoronaviruses found in bats and pangolins.

Another characteristic of SARS-CoV-2 is in its deficient amount of CpG dinucleotides. CpG is one of four pairs of nucleotides that make up DNA and RNA. CpG refers to a cytosine nucleotide followed by a guanine nucleotide.

This observation is important because one of nature’s weapons, the zinc finger antiviral protein (ZAP), binds to CpG dinucleotides. In response, RNA viruses infecting mammals have evolved genetic codes with fewer CpG dinucleotides, thus avoiding contact with the antiviral trap.

By surveying known coronaviruses for this feature, Xia probed alphacoronavirus the paper describes as “a virulent canine coronavirus possessing the most extreme CpG deficiency, comparable to that observed in SARS-CoV-2.”

Additionally, ACE2 — the enzyme that SARS-CoV-2 binds to in order to infect a cell — is more abundant in the animal gut than in the lungs.

“For the reasons given above, canine digestive system is one of the top candidates for a SARS-CoV-2 progenitor to evolve a low-CpG genome,” Xia said.

Imagine: Stray dogs in the wet market could have consumed bat meat infected with betacoronaviruses. The disease would easily spread from the gut to the lungs of an animal known for licking its own rear.

Although there have been no confirmed cases of pets contracting the disease in the U.S., the U.S. Centers for Disease Control and Prevention advises sick humans to avoid contact with the animals as well as humans. Likewise, pets are unlikely to catch the disease from infected wild dogs since they rarely encounter one another.

“Given that stray dogs typically do not interact with pet dogs, mutual transmission should be very rare,” Xia explained. “Also, dogs have relatively high mRNA expression of the ZAP protein (zinc finger antiviral protein) in the lung than in the intestine.”

Dogs are therefore still more likely to carry coronaviruses in their gut than in their lungs.

ADiscovery Grant from Natural Science and Engineering Research Council of Canada funded this study.

Xia said the search for the origin of the virus is important in terms of developing an efficient vaccine and preventing future outbreaks. But it should not be misconstrued as evidence for political prosecution.

“A person who was unfortunate to experience a bad zoonotic transmission is not supposed to bear the blame. In the current situation, it would be ridiculous for the world to blame China,” Xia said.

“Scientists aim to trace the origin of viral diseases, not to identify who is to blame,” Xia added. “The blaming game could be played by the few ignorant politicians but should not be practiced by the general public who know better.”

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