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SERINC5 Potently Restricts Retrovirus Infection In Vivo .

Research paper by Uddhav U Timilsina, Supawadee S Umthong, Brian B Lynch, Aimee A Stablewski, Spyridon S Stavrou

Indexed on: 16 Jul '20Published on: 16 Jul '20Published in: mBio



Abstract

The ine orporator (SERINC) proteins are multipass transmembrane proteins that affect sphingolipid and phosphatidylserine synthesis. Human SERINC5 and SERINC3 were recently shown to possess antiretroviral activity for a number of retroviruses, including human immunodeficiency virus (HIV), murine leukemia virus (MLV), and equine infectious anemia virus (EIAV). In the case of MLV, the glycosylated Gag (glyco-Gag) protein was shown to counteract SERINC5-mediated restriction in experiments and the viral envelope was found to determine virion sensitivity or resistance to SERINC5. However, nothing is known about the function of SERINC5. Antiretroviral function of a host factor is not always associated with antiretroviral function Using SERINC5 mice that we had generated, we showed that mouse SERINC5 (mSERINC5) restriction of MLV infection is influenced not only by glyco-Gag but also by the retroviral envelope. Finally, we also examined the function of the other SERINC gene with known antiretroviral functions, SERINC3. By using SERINC3 mice, we found that the murine homologue, mSERINC3, had no antiretroviral role either or To our knowledge, this report provides the first data showing that SERINC5 restricts retrovirus infection and that restriction of retrovirus infectivity is dependent on the presence of both glyco-Gag and the viral envelope. This study examined for the first time the function of the ine orporator (SERINC) proteins during retrovirus infection. SERINC3 and SERINC5 (SERINC3/5) restrict a number of retroviruses, including human immunodeficiency virus 1 (HIV-1) and murine leukemia virus (MLV), by blocking their entry into cells. Nevertheless, HIV-1 and MLV encode factors, Nef and glycosylated Gag, respectively, that counteract SERINC3/5 We recently developed SERINC3 and SERINC5 knockout mice to examine the function of these genes. We found that SERINC5 restriction is dependent on the absence of glycosylated Gag and the expression of a specific viral envelope glycoprotein. On the other hand, SERINC3 had no antiviral function. Our findings have implications for the development of therapeutics that target SERINC5 during retrovirus infection. Copyright © 2020 Timilsina et al.