A genetic analysis of SARS-CoV-2 and related coronaviruses suggests the pandemic may have originated in the digestive tracts of dogs before jumping to humans.
Coronaviruses are a large family of viruses present in both animals and humans. Rarely, a coronavirus that infects an animal evolves to make humans sick, thus creating a new, or novel, coronavirus like SARS-CoV-2, the coronavirus responsible for COVID-19 cases. It is largely believed that this virus jumped from bats to humans, but experts have wondered if another species served as an intermediary between the two. Some experts have proposed this gap was bridged by snakes or pangolins, but new findings published in Molecular Biology and Evolution suggest it was stray dogs that consumed the dead carcasses of infected bats.
Xuhua Xia, a professor of biology at the University of Ottawa in Canada, studied the molecular signatures of the coronavirus across different species, specifically examining 1,252 betacoronavirus genomes recorded in the database of genetic sequences, GenBank. SARS-CoV-2 and the closely related bat coronavirus (BatCov RaTG13) were found to share 96 percent of the genetic sequence and also the lowest amounts of CpG – a viral “signpost” that the human immune system targets – among the related coronavirus, suggesting the human form of the virus evolved from the one that infects bats.
When a virus invades a host, there are visible changes in the genomes of the virus from where the host’s immune system attacked. Mammals have what is known as the zinc finger antiviral protein (ZAP), a key antiviral protein that patrols the human lungs and stops a virus from multiplying, further degrading its genome. In RNA viruses like SARS-CoV-2, the ZAP specifically targets CpG dinucleotides within the virus’ RNA genome – but in some cases, the virus can strike back. Single-stranded coronaviruses like SARS-CoV, the virus responsible for the severe acute respiratory syndrome (SARS) outbreak in 2002, reduce CpG signs, making ZAP inefficient. In essence, levels of CpG can help trace a virus’s evolutionary history.
"Think of a decreased amount of CpG in a viral pathogen as an increased threat to public health, while an increased amount of CpG decreases the threat of such viral pathogens," said Xia. "A virus with an increased amount of CpG would be better targeted by the host immune system, and result in reduced virulence, which would be akin to natural vaccines."
When the data was applied to genetic information found in canine coronaviruses (CCoVs) – a highly contagious intestinal disease around the world – CpG values were similar to both those seen in SARS-CoV-2 and BatCoV RaTG13. Similarly, the cell receptor for SARS-CoV-2 entry is believed to be human made in the human digestive system, indicating that digestive tracts may be a likely target for coronavirus infection. Dogs who lick their anal and genital areas could facilitate viral transmission from the digestive tract, a theory that is evidenced by both animal and human fecal samples showing traces of SARS-CoV-2.
"While the specific origins of SARS-CoV-2 are of vital interest in the current world health crisis, this study more broadly suggests that important evidence of viral evolution can be revealed by consideration of the interaction of host defenses with viral genomes, including selective pressure exerted by host tissues on viral genome composition," said Xia.