Influence of Different Glycoproteins and of the Virion Core on SERINC5 Antiviral Activity.

William E Diehl,Massimo Pizzato,Pyae P Kyawe,Mehmet H Guney,Teresa Vanzo,Jeremy Luban,Judith M White

doi:10.3390/v13071279

Abstract

Host plasma membrane protein SERINC5 is incorporated into budding retrovirus particles where it blocks subsequent entry into susceptible target cells. Three structurally unrelated proteins encoded by diverse retroviruses, human immunodeficiency virus type 1 (HIV-1) Nef, equine infectious anemia virus (EIAV) S2, and ecotropic murine leukemia virus (MLV) GlycoGag, disrupt SERINC5 antiviral activity by redirecting SERINC5 from the site of virion assembly on the plasma membrane to an internal RAB7+ endosomal compartment. Pseudotyping retroviruses with particular glycoproteins, e.g., vesicular stomatitis virus glycoprotein (VSV G), renders the infectivity of particles resistant to inhibition by virion-associated SERINC5. To better understand viral determinants for SERINC5-sensitivity, the effect of SERINC5 was assessed using HIV-1, MLV, and Mason-Pfizer monkey virus (M-PMV) virion cores, pseudotyped with glycoproteins from Arenavirus, Coronavirus, Filovirus, Rhabdovirus, Paramyxovirus, and Orthomyxovirus genera. SERINC5 restricted virions pseudotyped with glycoproteins from several retroviruses, an orthomyxovirus, a rhabdovirus, a paramyxovirus, and an arenavirus. Infectivity of particles pseudotyped with HIV-1, amphotropic-MLV (A-MLV), or influenza A virus (IAV) glycoproteins, was decreased by SERINC5, whether the core was provided by HIV-1, MLV, or M-PMV. In contrast, particles pseudotyped with glycoproteins from M-PMV, parainfluenza virus 5 (PIV5), or rabies virus (RABV) were sensitive to SERINC5, but only with particular retroviral cores. Resistance to SERINC5 did not correlate with reduced SERINC5 incorporation into particles, route of viral entry, or absolute infectivity of the pseudotyped virions. These findings indicate that some non-retroviruses may be sensitive to SERINC5 and that, in addition to the viral glycoprotein, the retroviral core influences sensitivity to SERINC5.

Highlights

human immunodeficiency virus type 1 (HIV-1) Nef is important for maximal virus replication in vivo and for progression to AIDS [1,2,3]
To determine which viral glycoproteins are sensitive to the antiviral activity of SERINC5, pseudotyped GFP-expressing HIV-1 vectors were produced in the presence or absence of SERINC5, and infectivity was assessed
The panel of glycoproteins examined for SERINC5 sensitivity included a diverse selection of retroviral Env glycoproteins, including those encoded by HIV-1, avian leukosis virus A (ALV-A), human endogenous retrovirus K

Summary

Introduction

HIV-1 Nef is important for maximal virus replication in vivo and for progression to AIDS [1,2,3]. Class I, and other molecules from the cell surface [4,5,6,7,8,9]. SERINC5 is incorporated into budding virions where it inhibits subsequent fusion of the virion membrane with target cell membranes. Nef counteracts SERINC5 by removing it from the cell surface so that it is not incorporated into nascent virions [18,19,20,21]. HIV-1 is not the only virus inhibited by SERINC5. Simian immunodeficiency viruses (SIV) lacking nef are inhibited by SERINC5 and SIV nef counteracts this inhibition [18]

Methods

Results

Conclusion