Abstract
BackgroundWe previously showed that the gM of HSV-1 could restrict the release of infectious HIV-1 from cells. In this study, we analyzed if the four HSV-1 glycoproteins (gD, gB, and gH/gL), which are the minimum glycoproteins required for HSV-1 entry, restricted the release of infectious HIV-1.ResultsOf these four glycoproteins, gD and gH/gL restricted the production of infectious HIV-1 from cells transfected with an infectious molecular clone of HIV-1 (strain NL4-3) while gB had no significant effect. Pulse-chase analyses indicated that gD did not affect the biosynthesis and processing of gp160 into gp120/gp41, the transport of the gp120/gp41 to the cell surface, or the release of HIV-1 particles from the cell surface. Our analyses revealed that gD was incorporated into HIV-1 virus particles while gp120/gp41 was excluded from released virus particles. Truncated mutants of gD revealed that the cytoplasmic domain was dispensable but that a membrane bound gD was required for the restriction of release of infectious HIV-1. Finally, cell lines expressing gD also potently restricted the release of infectious virus.ConclusionsDue to its ability to exclude HIV-1 gp120/gp41 from maturing virus, gD may provide a useful tool in deciphering mechanisms of Env incorporation into maturing virus particles.
Highlights
We previously showed that the gM of herpes simplex virus type 1 (HSV-1) could restrict the release of infectious human immunodeficiency virus type 1 (HIV-1) from cells
Due to its ability to exclude HIV-1 gp120/gp41 from maturing virus, gD may provide a useful tool in deciphering mechanisms of Env incorporation into maturing virus particles
We chose to express gH and gL together as previous studies have shown expression of both proteins are necessary for optimal folding and transport to the cell surface, otherwise the proteins are unstable [18, 19]. 293 cells were transfected with the empty pcDNA3.1(+) vector or one expressing HSV-1 gB, gD, or gH/gL
Summary
We previously showed that the gM of HSV-1 could restrict the release of infectious HIV-1 from cells. Human herpes virus 1 (HHV-1 or HSV-1) encodes for at least 13 envelope glycoproteins, several of which are incorporated into mature virions Of these viral glycoproteins, four glycoproteins (gB, gD and the heterodimer gH/gL) have been implicated in HSV fusion and entry [1,2,3]. GB binding to HSPG is insufficient for entry and requires the interaction between the receptor binding protein gD and either one of three specific cell surface receptors: (a) herpesvirus entry mediator (HVEM); (b) nectin-1; or (c) heparan sulfate modified by 3-O-sulfotransferases [5,6,7,8,9,10,11,12,13,14] The latter event triggers the membrane fusion process that is mediated by gB and gH/gL [2, 15, 16]. The gB trimer and gH/gL heterodimer are conserved across the Family Herpesviridae while the receptor-binding gD varies among the family members
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