New UB research reveals how host cells work to block the entry of SARS-CoV-2 and, in turn, how the virus attacks back.
The findings highlight important features about cellular interactions between the virus and the host, and help develop new approaches to treatment for both SARS-CoV-2, the virus that causes COVID-19 and HIV. How can they be exploited to do so?
The research was reported by virologists in the Jacobs School of Medicine and Biomedical Sciences at UB and published May 26 in Nature Communications.
“We are interested in understanding how host cells defend against an invading viral pathogen,” says Spiridon Stavro, assistant professor of microbiology and immunology in the Jacobs School and corresponding author on the paper.
The team focused on a host gene called serine incorporator 5 (SERINC5), which is potentially antiviral against HIV-1, the most prevalent form of the virus. They found that this gene also exhibits potent antiviral activity against SARS-CoV-2 and, interestingly, it uses the same mechanism to inhibit both SARS-CoV-2 and HIV.
“We were surprised that SERINC5 also inhibits SARS-CoV-2, as this factor was primarily known to inhibit retroviruses,” says Uddhav Timilsina, a postdoctoral researcher in the Stavrou lab and first author of the study.
“The most surprising thing we observed is that SERINC5 uses a conserved mechanism to inhibit both HIV-1 and SARS-CoV-2, viruses that are quite different and are responsible for the current pandemics,” said Stavro. it is said. “This reflects a real host-pathogen conflict and emphasizes the importance of SERINC5 as an antiviral gene.”
The UB researchers were also amazed by what they discovered about how the virus reacts to SERINC5.
“Both HIV-1 and SARS-CoV-2 encode factors that counteract SERINC5 using similar mechanisms,” explains Stavro. “This again shows that SERINC5 is a very important antiviral host factor, because two very different viruses express virulence factors – in the case of SARS-CoV-2 it is a helper protein called SARS-CoV-2 ORF7a – Which is to thwart the antiviral effect. by host cells. ,
They report that this helper protein expressed to combat SERINC5 functions by preventing SERINC5 from being incorporated inside complete viral particles as they are generated and released from infected cells.
“Therefore, to overcome the host intrinsic immune response, SARS-CoV-2 encodes an antiviral factor (ORF7a) to counteract SERINC5,” says Stavro.
The findings are beneficial for further studies on the biology of SARS-CoV-2, as the role of the helper protein in the virus is not well understood.
“Furthermore, the fact that SERINC5 acts on two very different viruses using the same mechanism allows future targeting of SERINC5 for therapeutic development not only for SARS-CoV-2, but could potentially be good for HIV-1 as well,” he says.
He added that the research demonstrates that the antiviral mechanisms used by host genes are highly conserved, as host factors often use the same mechanisms to counteract very different viruses.
“It will be interesting to know whether the antiviral effect of SERINC5 extends to other viruses,” Timilsina says.
“The virus and the host are in this eternal arms race, in which both try to outdo each other,” notes Stavro. “Understanding more about how the arms race works could help us in our effort to blunt the effects of both the SARS-CoV-2 and HIV pandemics.”
Stavrou and Timilsina’s co-authors were Supawadi Umthong, postdoctoral fellow, and Emily B. Ivey and Brandon Waxman, doctoral candidates, are all from the Department of Microbiology and Immunology.
The work was supported by the National Institutes of Health.