New research from the UB reveals valuable information about how host cells work to block the entry of SARS-CoV-2 and, in turn, how the virus counterattacks.
The findings reveal important features about the cellular interactions between the virus and the host, and how they could be exploited to develop new treatment methods for both SARS-CoV-2, the virus that causes COVID-19, and to HIV.
The research was reported by virologists at the Jacobs School of Medicine and Biomedical Sciences at the UB and published on May 26 in Nature Communications.
“We are interested in understanding how host cells mount a defense against an invasive viral pathogen,” says Spyridon Stavrou, assistant professor of microbiology and immunology at Jacobs School and corresponding author of the paper.
The team focused on the host gene called Serine Incorporator 5 (SERINC5), which is potent antiviral against HIV-1, the most common form of the virus. They found that this gene also has potent antiviral activity against SARS-CoV-2 and, interestingly, uses the same mechanism to block both SARS-CoV-2 and HIV.
“We were surprised that SERINC5 also blocked SARS-CoV-2, as this factor was known to restrict retroviruses,” said Uddhav Timilsina, a postdoctoral researcher at the Stavrou Laboratory and lead author of the study.
“The most amazing thing we noticed is that SERINC5 uses a conserved mechanism to restrict both HIV-1 and SARS-CoV-2, viruses that are quite different and are responsible for current pandemics,” says Stavrou. “This shows a good faith fight with the host pathogen and emphasizes the importance of SERINC5 as an antiviral gene.”
UB researchers were also surprised by what they found out about how the virus responds to SERINC5.
“Both HIV-1 and SARS-CoV-2 encode factors that counteract SERINC5 by identical mechanisms,” explains Stavrou. “This again proves that SERINC5 is a very important antiviral host factor, as two very different viruses express viral factors – in the case of SARS-CoV-2 it is an accessory protein called SARS-CoV-2 ORF7a – to frustrate the mounted antiviral effect by host cells ”.
They report that this accessory protein expressed to fight SERINC5 works by blocking SERINC5 from entering the whole viral particles as they are produced and released from the infected cells.
“Therefore, to overcome the intrinsic immune response of the host, SARS-CoV-2 encodes an antiviral factor (ORF7a) to counteract SERINC5,” says Stavrou.
The findings are beneficial for further studies on the biology of SARS-CoV-2, as the role of accessory proteins in the virus has not been well understood.
“Furthermore, the fact that SERINC5 acts on two very different viruses using the same mechanism allows us to target SERINC5 in the future for the development of therapies that may be good not only for SARS-CoV-2, but potentially for HIV- 1 “. he says.
He adds that research shows that the antiviral mechanisms used by host genes are highly conserved, as host factors often use the same mechanism to counteract very different viruses.
“It will be interesting to know if the antiviral effect of SERINC5 extends to other viruses,” says Timilsina.
“Viruses and the host are in this eternal arms race, in which they both try to make fun of each other,” Stavrou said. “Understanding more about how this arms race works can only help us in our efforts to mitigate the effects of both the SARS-CoV-2 pandemic and HIV.”
Co-authors with Stavrou and Timilsina are Supawadee Umthong, a postdoctoral fellow, and Emily B. Ivey and Brandon Waxman, PhD candidates, all from the Department of Microbiology and Immunology.
The work was supported by the National Institutes of Health.