Genetic Quirk Could Explain How Pangolins Can Tolerate Coronaviruses

Pangolins possess a genetic quirk that may offer them some kind of protection against coronaviruses like COVID-19, according to scientists. If these suspicions prove to be correct, researchers hope it could help pave the way for new treatments to help people infected with the novel coronavirus.

The genetic difference in question is the absence of two genes (ZBP1 and IFIH1) that, in other mammals, warn the body of any intruders (or viruses) in a similar fashion to a smoke detector raising the alarm if it senses smoke particles. While that in itself is not an advantage, scientists know that pangolins are carriers of COVID-19 and other coronaviruses and yet, they appear to be able to tolerate these pathogens—they just don't know how exactly that is. If the mechanism to which they can tolerate these viruses can be identified, it could help guide possible treatments for COVID-19 and others, the study published in Frontiers in Immunology suggests.

The reason for this is that in humans, the immune response to SARS-CoV-2—the virus responsible for COVID-19—can exacerbate the severity of infection by triggering an event called a cytokine storm. In short, the body goes into overdrive and attacks itself, causing more harm in trying to rid the body of the intruder than the virus causes itself.

In contrast, pangolins appear to have evolved a tolerance for the virus that enables them to survive with the pathogen. The dampened immune response may mean that the virus is not efficiently eliminated from the body, but the trade-off is that it reduces damage caused by the body's immune system.

"Our study suggests that pangolins respond to coronaviruses differently from other mammals including humans," co-author Dr. Leopold Eckhart, of the Medical University of Vienna, told Newsweek.

"We believe that the defense against RNA viruses, such as corona and influenza viruses, may be decreased in intensity or altered in its timing in pangolins."

The researchers believe that the pharmaceutical suppression of gene signaling could offer a potential route for treatment in people who develop a severe response to COVID-19. Eckhart said moderating an overzealous immune system could be achieved by dialing down the intensity of the defense reaction or by adjusting the timing. However, he warns that treatments along these lines could increase the risk of secondary infections.

The findings pose an additional potential significance—animals that can tolerate pathogens (like bats) could be important reservoirs for zoonotic diseases that can jump into new species, just as COVID-19 did in humans. While scientists have not identified the intermediary host that first transmitted SARS-CoV-2 to people—and some say it is unlikely they ever will—it emphasizes the risks of close contact with pangolins and the issue of wet markets.

"It is surprising that pangolins lack a part of the antiviral defense system that was previously considered essential for all mammals," said Eckhart. "A comparable degeneration of other antiviral genes was previously found in bats and bats are known to be an important reservoir of zoonotic viruses.

"Therefore, it is conceivable that pangolins are also special hosts of viruses."

However, he stresses this is a hypothesis and needs to be explored further.

Malayan pangolin conviscated by Malaysian officials
A Malayan pangolin is seen out of its cage after being confiscated by the Department of Wildlife and Natural Parks in Kuala Lumpur, 08 August 2002. Scientists say pangolins lack two genes common in other mammals. Determining how they can tolerate coronaviruses may pave the way for COVID-19 treatment. JIMIN LAI/AFP/Getty

The study, published in Frontiers of Immunology this week, involved the genetic analysis of three species of pangolin; the Malayan, or Sunda, (Manis javanica), Chinese (Manis pentadactyla) and tree pangolin (Manis tricuspis). They were compared to analyses of humans, cats, dogs and cattle.

While the researchers were able to identify certain missing genes, they still do not understand how it is that pangolins can survive the coronavirus. Eckhart and his colleagues plan to continue research on immune defense genes in diverse species to improve understanding of different species' responses to pathogens like SARS-CoV-2.

"A better understanding of different antiviral defense strategies may help in the clinical management of COVID-19 and of the next emerging infectious diseases," he said.