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

Surprisingly, we observed that particular glycoproteins displayed different sensitivity to the antiviral effects of SERINC5 depending on the viral core onto which they were pseudotyped. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 cores pseudotyped with RD114 Env, while 7.5-fold and 4.3-fold inhibitions were observed for RD114 pseudotypes of MLV and HIV cores, respectively. A previous report demonstrated similar magnitude inhibition for RD114-pseudotyped MLV by endogenous SERINC activity (24). Regardless, RD114 showed little sensitivity to SERINC5 when pseudotyped onto HIV-1 cores. Neutralization by monoclonal antibodies that target the membrane-proximal domain of HIV-1 glycoprotein is altered by the presence of SERINC5 (19, 25) . Given that MA, the membrane proximal domain of gag makes contacts with the retroviral TM (40, 41), one can imagine that SERINC5 has the potential to influence interactions between MA and TM in the HIV-1 virion that are essential for infectivity. In similar fashion, SERINC5 might influence retroviral core interactions by the heterologous glycoproteins tested here, for which SERINC5 restriction activity was core-dependent, i.e., the rabies virus, MPMV, and RD114 glycoproteins. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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