Mol Biol Evol: New research claims stray dogs or intermediate hosts for SARS-CoV-2, Cambridge experts believe “unreliable”

Mol Biol Evol: New research claims stray dogs or intermediate hosts for SARS-CoV-2, Cambridge experts believe “unreliable”
April 17, 2020 No Comments News

Since the outbreak of the new coronavirus (SARS-CoV-2), researchers have been exploring how this virus, which has infected more than 2 million people worldwide, was initially transmitted to humans.From pangolins to snakes to tree shrews and ferrets, although many studies have tried to solve the mystery of the intermediate host of SARS-CoV-2, the viruses isolated from these animals are relatively large compared to SARS-CoV-2. The difference, this traceability continues.On April 14, local time, a research report published in “Molecular Biology and Evolution” provided a new conjecture for the origin and initial spread of SARS-CoV-2.https: // tracking the characteristics of different coronaviruses, Xia Xuhua, a professor of biology at the University of Ottawa, suggested that stray dogs may be the origin of the pandemic. The ancestors of SARS-CoV-2 and their close relatives, the bat coronavirus, first infected the intestines of canines, followed by rapid mutation and evolution in canines, and took the opportunity to spread to humans. Researchers believe that it may be necessary to detect stray dogs for viruses.Virus immune escape makes it more threatening to public healthIn this study, the researchers first traced the source of the virus “fighting”.Generally speaking, when a virus invades a host, the human immune system will take action to resist its invasion. Zinc finger antiviral protein (ZAP), as a key antiviral sentinel protein possessed by humans and mammals, will “patrol” in the human body, especially in lymphocyte-rich lungs, spleen, bone marrow, lymph nodes High expression.The CpG dinucleotide is a road sign used by the human immune system to find and eliminate the virus. Once it is found, ZAP will specifically bind to the CpG dinucleotide in the viral RNA genome through the RNA binding domain, thus preventing the virus from in vivo Multiply.However, since the virus can successfully invade the human body, it means that it has found a way to avoid ZAP-mediated cellular anti-virus defense. To date, many studies have demonstrated that there is a correlation between the decrease in CpG in the viral RNA genome and the increase in virulence. Analysis of the single-stranded coronavirus SARS-CoV shows that this virus can avoid “censorship” by reducing CpG, and another RNA virus, the HIV virus, also escapes the human anti-virus defense mechanism in this way. .Based on this, the researchers examined all 1252 full-length β-coronavirus genomes deposited in GenBank to date and found that SARS-CoV-2 and its closest related relative, the bat coronavirus (BatCoV RaTG13), in its coronavirus close relative The CpG content is the lowest. This also means that the virus has become more covert and poses a greater threat to public health. However, if you increase the CpG in the virus, it will be more likely to be “stared” by the immune system, and the threat will also be reduced, similar to the “natural vaccine”.Canines are more likely to be the source of a “pandemic”Subsequently, the researchers used the CpG detection tool to re-detect the Middle East Respiratory Syndrome Coronavirus (MERS) that originated in camels and found that the viral genome that infected the camel digestive system had a lower CpG content than the viral genome that infected the camel respiratory system.After analyzing the entire alpha coronavirus (AlphaCoV) genome, including canine coronaviruses (CCoVs), the researchers found that only CCoVs were similar to the CpG values ​​observed in SARS-CoV-2 and BatCoV RaTG13. In addition, similar to camels, the CpG value of CCoVs in the digestive system of canines is much lower than that observed in the respiratory system.Previous studies have shown that the cell receptor for SARS-CoV-2 entering the cell is ACE2, which is commonly expressed in the human digestive system, with the highest expression in the small intestine and duodenum, indicating that the mammalian digestive system may be The main target of coronavirus infection.Initially, some studies suggested that pangolins are an intermediate host for the spread of SARS-CoV-2 to humans. However, in this study, the researchers analyzed nine SARS-CoV-2-like genomes isolated and sequenced from the pangolin and found that the highest sequence coverage ICpG value was 0.3929, which was close to the SARS-CoV-2 genome. The lowest point of the CpG value observed in. This shows that SARS-CoV-2, BatCoV-RaTG13 and pangolin may have a common low ICpG ancestor or have evolved low CpG values.Based on these evidences, the researchers proposed a hypothesis: canines eat bat meat to infect their intestines; viruses rapidly evolve in their intestines, resulting in a decrease in CpG values, and the canine habit of licking the anus Let the virus spread from the digestive system to the respiratory system; the reduced viral genome CpG caused the immune escape of the virus, and gradually led to today’s pandemic situation.The “Stray Dog Intermediate Host” theory was questioned by Cambridge expertsBecause there is no direct evidence, this study has been questioned by some experts. James Wood, an expert in veterinary medicine at the University of Cambridge, said: “I have a hard time understanding how the authors draw conclusions from this study or make a lot of assumptions, not to mention that the virus that caused COVID-19 may have evolved through dogs. . “Caroline Allen, chief veterinarian of the RSPCA, said: “It is important to note that this is just a theory. There is currently no evidence that dogs are the origin of this virus, nor evidence that they are spreading among humans. COVID- It played a role in the spread of 19. The most important thing is that people do n’t give up on them, let alone cause harm to pets or stray dogs because of some theoretical papers. “In addition, on April 8, a study in Science related to animal infections suggested that cats and ferrets are highly susceptible to new coronavirus, while dogs are less likely to be infected with new coronavirus.In short, this new study provides a reference for us to trace the origin of SARS-CoV-2, but it must be made clear that this is just a hypothesis, and there is no direct conclusive evidence that stray dogs are intermediate hosts. At the same time, even if we finally find an intermediate host, it does not mean that we can blame these animals for causing this “pandemic” worldwide, because the main reason for the widespread spread of the epidemic is the spread between people.

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