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

Due to observed differences in SERINC5 sensitivity with M-PMV pseudotypes of HIV-1 and MLV cores, we next tested for SERINC5 antiviral activity against our panel of glycoproteins pseudotyped onto M-PMV cores ( Figure 3B and Table 1 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/780577 doi: bioRxiv preprint DISCUSSION Initial reports indicated that the viral glycoprotein is a determinant of sensitivity to SERINC5 antiviral activity (17, 18, 25, 26) and suggested that viral glycoproteins which mediate fusion via a pH-dependent, endocytic entry pathway are resistant to SERINC5 antiviral activity (17, 24) . Here, to examine these issues further, pseudotypes using glycoproteins from diverse families of enveloped viruses were assessed for sensitivity to restriction by SERINC5. We observed that SERINC5 restricted virions pseudotyped with glycoproteins from several retroviruses (HIV-1, A-MLV, RD114, and M-PMV), influenza A (Orthomyxoviridae), and rabies (Rhabdoviridae). To our knowledge, this is the first time antiviral activity of SERINC5 has been described for a non-retroviral glycoprotein. As the glycoproteins of these viruses were studied as retroviral pseudotypes, it remains to be established if the infectivity of authentic influenza or rabies viruses are affected by SERINC5, or other SERINC family members.