Incorporation of PSGL-1 into HIV-1 Virions via Env Exclusion Mechanism Blocks Infectivity

Abstract

Human immunodeficiency virus (HIV), a virus that causes acquired immune deficiency syndrome (AIDS). HIV primarily targets immune cells, specifically CD4+ T lymphocytes, for infection, through binding to the CD4 receptor and co-receptors, either CCR5 or CXCR4, on the cell surface. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like surface glycoprotein, is primarily expressed on immune cells and has a role in inflammation. PSGL-1 has been recognized as an HIV restriction factor by blocking HIV infectivity through virion incorporation that sterically hinders virion attachment to target cells. PSGL-1 also inhibits the incorporation of HIV Env into virions by spatially excluding HIV Env. In this study, we have tested the efficiency to PSGL-1 in blocking HIV-1 infectivity. In order to compare the HIV-1 infection, we have packaged a pseudotyped virus in a Lenti vector that expresses green fluorescent protein (GFP), labeled Lenti-turbo-GFP (LTG) and Lenti-turbo-GFP-PSGL-1 (LTGP), along with HIV components such as gag-pol and vesicular stomatitis virus G glycoprotein (VSV-G), as Env in a human cell line, HEK293T cells. On three days of post-infection, we analyzed our data using fluorescent microscopy and flow cytometry, and results suggest a significant decrease in the HIV infection with LTGP virus that expresses PSGL-1. Hence, we could effectively block HIV-1 infection by PSGL-1 in HEK293T cells using LTGP viruses. Therefore, we conclude that PSGL-1 could be used as factor for broad-spectrum HIV-1 restriction.