Structural Domains of the Herpes Simplex Type 1 gD Protein that Restrict HIV-1 Particle Infectivity.

Autor:	Arachchige SP; Department of Microbiology, Molecular Genetics and Immunology, 2000 Hixon Hall, 3901 Rainbow Blvd. University of Kansas Medical Center, Kansas City, Kansas USA 66160 Phone: 913-588-5558 Fax: 913-588-7295., Henke W; Department of Microbiology, Molecular Genetics and Immunology, 2000 Hixon Hall, 3901 Rainbow Blvd. University of Kansas Medical Center, Kansas City, Kansas USA 66160 Phone: 913-588-5558 Fax: 913-588-7295., Kalamvoki M; Department of Microbiology, Molecular Genetics and Immunology, 2000 Hixon Hall, 3901 Rainbow Blvd. University of Kansas Medical Center, Kansas City, Kansas USA 66160 Phone: 913-588-5558 Fax: 913-588-7295., Stephens EB; Department of Microbiology, Molecular Genetics and Immunology, 2000 Hixon Hall, 3901 Rainbow Blvd. University of Kansas Medical Center, Kansas City, Kansas USA 66160 Phone: 913-588-5558 Fax: 913-588-7295 estephen@kumc.edu.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2021 Mar 25; Vol. 95 (8). Date of Electronic Publication: 2021 Feb 03.
DOI:	10.1128/JVI.02355-20
Abstrakt:	Previously, we showed that the presence of the herpes simplex virus type 1 (HSV-1) gD glycoprotein but not gB potently restricted HIV-1 particle infectivity. This restriction was characterized by incorporation of HSV-1 gD and the exclusion of the HIV-1 gp120/gp41 from budding virus particles. To determine the structural domains involved in gD restriction of HIV-1, a series of deletion mutants and chimeric proteins between gD and the non-restrictive gB were generated. Our results show that deletion of the cytoplasmic tail domain (CTD) of gD or that replacement of the transmembrane domain (TMD) with the TMD from gB slightly reduced restriction activity. However, replacement of the gD CTD with that of gB resulted in lower cell surface expression, significantly less incorporation into HIV-1 particles, and inefficient restriction of the release of infectious HIV-1. Analysis of gB/gD chimeric proteins revealed that removal of the gB CTD or replacement with gD CTD resulted in enhanced surface expression and an increase in restriction activity. Finally, we show that expression of gD without other HSV-1 proteins resulted in gD fractionation into detergent resistant membranes (DRM) and that gD co-localized with the raft marker GM1, which may partially explain its incorporation into budding virus particles. Taken together, our results suggest that expression of gD at the cell surface is likely a major factor but that other intrinsic properties are also involved in the gD-mediated restriction of HIV-1 particle infectivity. IMPORTANCE Previously, we showed that unlike the HSV-1, the presence of the gD glycoprotein in virus producer cells but not gB potently restricted HIV-1 particle infectivity. To better understand the relationship between cell surface expression, virus incorporation and restriction of HIV-1, we analyzed a series of deletion mutants and chimeric proteins in which domains of gD and gB were swapped. Our results indicate that: a) gD/gB chimeras having the cytoplasmic domain (CTD) of gB significantly reduced cell surface expression, release from cells, incorporation into virus, and reduced HIV-1 restriction; b) removal of the gB CTD or replacement with the gD CTD resulted in better surface expression, incorporation into HIV-1, and enhanced restriction; and c) the transmembrane domain of gB can influence transport and ultimately effect incorporation of gB into HIV-1. Overall, these data support a role for gD surface expression as crucial to restriction of infectious HIV-1 release. (Copyright © 2021 American Society for Microbiology.)
Databáze:	MEDLINE
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