SARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5

• Published in: Nature communications Vol. 13; no. 1; p. 2935
• Main Authors: Timilsina, Uddhav, Umthong, Supawadee, Ivey, Emily B., Waxman, Brandon, Stavrou, Spyridon
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 13/31; 13/89; 14; 14/19; 14/34; 38/22; 38/23; 38/35; 38/5; 38/70; 38/77; 38/88; 38/89; 38/90; 45/22; 45/29; 49/23; 631/326/596/2557; 631/326/596/4130; 82/51; 82/80; 96/31; Antiviral agents; Antiviral Agents - pharmacology; Biosynthesis; Cell fusion; Coronaviruses; COVID-19; HIV; HIV Infections; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Infectivity; Membrane Proteins; multidisciplinary; Progeny; Proteins; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Viral diseases; Virion - physiology; Virions; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30609-9

Serine Incorporator 5 (SERINC5), a cellular multipass transmembrane protein that is involved in sphingolipid and phosphatydilserine biogenesis, potently restricts a number of retroviruses, including Human Immunodeficiency Virus (HIV). SERINC5 is incorporated in the budding virions leading to the inhibition of virus infectivity. In turn, retroviruses, including HIV, encode factors that counteract the antiviral effect of SERINC5. While SERINC5 has been well studied in retroviruses, little is known about its role in other viral families. Due to the paucity of information regarding host factors targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), we evaluated the effect of SERINC proteins on SARS-CoV-2 infection. Here, we show SERINC5 inhibits SARS-CoV-2 entry by blocking virus-cell fusion, and SARS-CoV-2 ORF7a counteracts the antiviral effect of SERINC5 by blocking the incorporation of over expressed SERINC5 in budding virions. SERINC5, is a cellular multipass transmembrane protein involved in sphingolipid and phosphatydilserine biogenesis and a known retroviral restriction factor. Here, Timilsina et al. show that SERINC5 is a host restriction factor for SARS-CoV-2 that prevents viral fusion during entry. Further they show that viral ORF7a counteracts SERINC5 anti-viral activity by blocking its incorporation into progeny virions.