Scientists of the Sanford Burnham Prebys have identified a number of human genes that fight infection with SARS-CoV-2, the virus that causes the COVID-19.
Knowing which genes help control viral infection can greatly help researchers understand the factors that influence disease severity and also suggest possible treatment options.
The study was published in the Molecular Cell magazine.
Genetic factors
The genes in question are related to interferon, the frontline fighters of the body's viruses.
"We wanted to gain a better understanding of the cellular response to SARS-CoV-2, including what causes a strong or weak response to infection," he says. Sumit K. Chanda, Ph.D., professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and lead author of the study.
We have gained new insights into how the virus exploits the human cells it invades, but we are still looking for its Achilles heel so that we can develop optimal antivirals.
The list of villains
Immediately after the pandemic began, doctors found that a weak interferon response to SARS-CoV-2 infection resulted in some of the most severe cases of COVID-19. This knowledge led Chanda and her collaborators to search for human interferon-stimulated genes (ISGs), which act to limit SARS-CoV-2 infection.
"We found that 65 ISGs controlled SARS-CoV-2 infection, including some that inhibited the virus's ability to enter cells, some that suppressed the production of RNA (which is the lifeblood of the virus), and one group of genes that inhibited the assembly of the virus, ”says Chanda. "What was also of great interest was the fact that some of the ISGs showed control of even unrelated viruses, such as seasonal flu, West Nile and HIV, which leads to AIDS."
A weapon against infection
"We identified eight ISG genes that inhibited SARS-CoV-1 and CoV-2 replication in the subcellular compartment responsible for protein packaging. This suggests that this vulnerable site could be exploited to eliminate viral infection," he says. Laura Martin-Sancho, first author of this study. "This is important information, but we still need to learn more about the biology of the virus and investigate whether the genetic variability within these ISGs is related to the severity of COVID-19."
As a next step, the researchers will examine the biology of SARS-CoV-2 variants that continue to evolve and threaten the effectiveness of vaccines.
"It is vitally important not to ease research efforts now that vaccines are helping to control the pandemic," Chanda concludes. “We have come this far and so soon thanks to investment in research. Our continued efforts will be particularly important when, not if, another viral outbreak will occur".
