The pandemic coronavirus SARS-CoV-2 (shown above) under certain conditions can mimic its genetic material into human cells, confirming COVID-19 diagnostic tests.
NIAID
By Jon Cohen
Science”s The COVID-19 report is supported by the Pulitzer Center and the Heising-Simons Foundation.
People who sometimes get COVID-19 later test positive for SARS-CoV-2, suggesting that their immune systems could not be attacked a second time by the crown virus. keep away or have an infectious disease. A study is now considering a different explanation in which the virus hides in an unexpected place. The work, which has only been reported in an introduction, suggests that the pandemic pathogen takes a leaf from HIV and other retroviruses and unifies its genetic code – but, importantly, only parts of it -. for human chromosomes. The phenomenon, if true and frequent, that ranges from false positives of active disease to false results from COVID-19 treatment studies could have a significant impact.
The current study only showed this integration in a lab basin, although it also cites published series data from people with SARS-CoV-2 infection that indicate its occurrence. The authors confirm that their results do not imply that SARS-CoV-2 establishes a permanent genetic residence in human cells to pump out new copies, as does HIV.
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Other scientists are divided on the importance of the new work and its relevance to human health, and some are very critical. “There are open-ended questions we need to address,” said molecular biologist Rudolf Jaenisch of the Massachusetts Institute of Technology (MIT), who led the work.
But some old retrovirologists are interested. “This is a very interesting molecular analysis and profiling with supporting data provided,” said Robert Gallo, who heads the Institute of Human Virology and looked at the new prospect posted at Scienceapplication. “I don’t think it’s a whole story to be sure … but as it is, I like it and I think it will be right.”
Each virus inserts its genetic material into the cells they infect, but it is usually separate from the DNA of the cell itself. The Jaenisch team, enthralled by reports of people taking a positive test for SARS-CoV-2 after recovering, questioned whether these interesting results revealed anything of an artifact. from the polymerase chain assay (PCR), which detects specific strains of virus in biological samples such as nasal swabs, even though they are fragmented and cannot extract new viruses. “Why do we have this poster, which can now be seen all over the place, long after the active disease has disappeared?” said Jaenisch, who collaborated with Richard Young’s laboratory at MIT.
To test whether the RNA genome SARS-CoV-2 could be incorporated into the DNA of our chromosomes, the researchers sequenced the gene for reverse transcriptase (RT), an enzyme that converts RNA to DNA, to human cells and the cells engineered with SARS-CoV-2. In one experiment, the researchers used the RT gene from HIV. They also donated RT using human DNA sequences called LINE-1 elements, which are remnants of old retroviral diseases and make up about 17% of the human genome. As a result of the cells making up the second part of the enzyme, some fragments of SARS-CoV-2 RNA were converted to DNA and incorporated into human chromosomes, the team reports in the pre- say, posted on bioRxiv on December 13th.
If the LINE-1 sequences naturally produce RT in human cells, SARS-CoV-2 synthesis may occur in people with COVID-19. This may occur in people coinfected with SARS-CoV-2 and HIV, too. Each condition can explain PCR detecting lingering of coronavirus genetic material in people with no real disease. And it could confuse studies of COVID-19 therapies that rely on PCR tests to measure changes in indirect measurements in the amount of infectious SARS-CoV-2 in the body.
David Baltimore, an expert at the California Institute of Technology who won the Nobel Prize for his role in the discovery of RT, says the new work is “impressive” and the results are “unexpected” but it is noteworthy that Jaenisch and his colleagues show that only fragments of the SARS-CoV-2 genome integrate. “Because it is part of the coronaviral genome, it cannot cause RNA or infectious DNA and so it appears to be biologically dead,” Baltimore says. “It is also unclear whether, in humans, the cells that harbor the posterior transcripts will stay around for a long time or die. The work raises a lot of interesting questions. ”
Scientist Melanie Ott, who studies HIV at the Gladstone Institute of Virology and Immunology, says the findings are “very encouraging” but need to be followed up with careful diagnosis. “I have no doubt that background resection can occur in vitro with optimal conditions,” Ott says. But she notes that SNA-CoV-2 RNA replication occurs in specific regions in the cytoplasm. “Whether it occurs in infectious cells and… leads to massive integration in the cell cloud is another question.”
Retrovirologist John Coffin of Tufts University says the new work is “credible,” noting that hard evidence shows that LINE-1 RT can allow viral substances to unite in humans, but it does not. he remains unsure. The evidence for SARS-CoV-2 strains in humans, Coffin says, “should be more robust,” and the in vitro tests performed by the Jaenisch team lack control it would have seen. Overall, I doubt the phenomenon has much biological relevance, despite the authors’ profiteering, ”says Coffin.
Zandrea Ambrose, a retrovirologist at the University of Pittsburgh, says this type of integration would be “very rare” if it did happen. She notes that LINE-1 elements in the human genome are rarely active. “It is not clear what the activity would be in different primary cell types called SARS-CoV-2,” she says.
One especially hard on Twitter, a postdoctoral researcher in a laboratory specializing in retroviruses, went so far as to call the findings of the introduction “a strong, dangerous, and largely unsupported application.” Jaenisch confirms that the paper clearly states the integration that the authors believe may lead to the production of infectious SARS-CoV-2. “Let’s assume that we can resolve these complaints completely, which I am trying to do,” says Jaenisch. “Maybe this isn’t a concern.”