Influence of different glycoproteins and of the virion core on SERINC5 antiviral activity

William E. Diehl; Mehmet H. Guney; Pyae Phyo Kyawe; Judith M. White; Massimo Pizzato; Jeremy Luban

Using this system, we tested the sensitivity of a number of retroviral Envs as well as representative glycoproteins from the Arenavirus, Coronavirus, Filovirus, Rhabdovirus, Paramyxovirus, and Orthomyxovirus genera. Consistent with previous findings, we observed that glycoprotein is a major determinant of SERINC5 sensitivity. While many glycoproteins were universally insensitive to the antiviral effects of SERINC5, the glycoproteins from NL4.3, A-MLV, and influenza were inhibited by SERINC5 in all viral core pseudotypes tested. No correlation was observed between SERINC5 sensitivity and the route of viral entry mediated by the viral glycoprotein. Unexpectedly, we also observed that sensitivity to SERINC5 antiviral activity for M-PMV, RD114, and rabies virus (RABV) glycoproteins depended on the retroviral core onto which they were pseudotyped. Our findings reveal that an interplay between virion core and glycoprotein determines the sensitivity to SERINC5 antiviral activity.