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

HIV-1 Nef, MLV glygoGag, and EIAV S2 counteract SERINC5 antiviral activity by removing SERINC5 protein from the cell surface and relocalizing it to an endosomal compartment (17, 18, 22) . The ability of a viral glycoprotein to re-localize a normally plasma membrane localized antiviral protein has been previously shown for HIV-2 Env and human BST2 (38). Thus, we reasoned that viral glycoproteins may confer resistance to SERINC5 activity by re-localizing SERINC5 to an internal membrane compartment. To test this, we compared SERINC5 incorporation into HIV-1 virus-like particles (VLPs) pseudotyped with the various glycoproteins shown in Fig 1A. We found that HIV-1 VLPs universally incorporated SERINC5 irrespective of the viral glycoprotein present ( Figure 2 ). In replicate blotting, only HERV-K Env showed a consistently lower level of SERINC5 incorporation into viral particles (data not shown). However, this observation is likely to be caused by pleiotropic effects of cells transfected with this glycoprotein, as cell growth was significantly reduced compared to other transfections, and reduced levels of Gag and GFP were also observed ( Fig. 2 , data not shown).