HSV-2- and HIV-1- permissive cell lines co-infected by HSV-2 and HIV-1 co-replicate HSV-2 and HIV-1 without production of HSV-2/HIV-1 pseudotype particles

Jérôme Legoff,Christophe Klein,Ali Si-Mohamed,Hakim Hocini,Martin Muggeridge,Hicham Bouhlal,Maxime Lecerf,Laurent Bélec

doi:10.1186/1743-422x-4-2

Abstract

BackgroundHerpes simplex virus type 2 (HSV-2) is a major cofactor of human immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission. In the present study, we investigated whether HIV-1 and HSV-2 may interact at the cellular level by forming HIV-1 hybrid virions pseudotyped with HSV-2 envelope glycoproteins, as was previously reported for HSV type 1.MethodsWe evaluated in vitro the production of HSV-2/HIV-1 pseudotypes in mononuclear CEM cells and epithelial HT29 and P4P cells. We analyzed the incorporation into the HIV-1 membrane of HSV-2 gB and gD, two major HSV-2 glycoproteins required for HSV-2 fusion with the cell membrane, in co-infected cells and in HIV-1-infected P4P cells transfected by plasmids coding for gB or gD.ResultsWe show that HSV-2 and HIV-1 co-replicated in dually infected cells, and gB and gD were co-localized with gp160. However, HIV-1 particles, produced in HIV-1-infected cells expressing gB or gD after transfection or HSV-2 superinfection, did not incorporate either gB or gD in the viral membrane, and did not have the capacity to infect cells normally non-permissive for HIV-1, such as epithelial cells.ConclusionOur results do not support the hypothesis of HSV-2/HIV-1 pseudotype formation and involvement in the synergistic genital interactions between HIV-1 and HSV-2.

Highlights

Herpes simplex virus type 2 (HSV-2) is a major cofactor of human immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission
It has been recently hypothesized that HIV-1 and HSV-1 may interact at the cellular level by the formation of HIV1 hybrid virions pseudotyped with herpes simplex virus type 1 (HSV-1) envelope glycoproteins [14,15]
Colocalization of HSV-2 gB and gD with gp160 in coinfected or transfected cells Prior evaluating the potential formation of pseuotyped particles, we first analyzed at the cellular level the coexpression of gB and gp160, or gD and gp160, in HIV-1 infected P4P cells superinfected by HSV-2, and in HIV-1infected P4P cells transfected by plasmids coding for gB or gD, by using confocal microscopy

Summary

Introduction

Herpes simplex virus type 2 (HSV-2) is a major cofactor of human immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission. Genital infection by herpes simplex virus type 2 (HSV-2) is considered one of the major cofactors favoring both sexual transmission and acquisition of the human immunodeficiency virus type 1 (HIV-1) [1] This assertion is based on several criteria as defined by Judith and Wasserheit [2], including mainly epidemiological evidence, biological plausibility, and ongoing intervention studies [1,3,4]. Two independant studies showed that cell-free culture supernatant from HIV-1 and HSV-1 dually infected lymphocyte cell lines was able to induce HIV-1 productive infection in cells normally resistant to HIV-1 infection, leading to the proposal that HIV-1 particles may acquire HSV-1 glycoproteins through budding at the cell surface [14,15] Such pseudotyped HIV-1 virions acquired new phenotypic properties with a larger cell tropism. In vivo observations obtained by electron microsopy from herpetic skin lesions showed that CD4 negative epidermal keratinocytes contained HIV-1 and HSV-1 particles, supporting the hypothesis of the presence of HIV-1 pseudotyped virions [16]

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