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Interaction between herpesvirus entry mediator and HSV-2 glycoproteins mediates HIV-1 entry of HSV-2-infected epithelial cells.

Hu, K; He, S; Xiao, J; Li, M; Luo, S; Zhang, M; Hu, Q (2017) Interaction between herpesvirus entry mediator and HSV-2 glycoproteins mediates HIV-1 entry of HSV-2-infected epithelial cells. J Gen Virol, 98. pp. 2351-2361. ISSN 1465-2099 https://doi.org/10.1099/jgv.0.000895
SGUL Authors: Hu, Qinxue

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Abstract

Herpes simplex virus type 2 (HSV-2) increases human immunodeficiency virus type 1 (HIV-1) acquisition and transmission via unclear mechanisms. Herpesvirus entry mediator (HVEM), an HSV-2 entry receptor, is highly expressed on HIV-1 target cells (CD4+ T cells) and may be incorporated into HIV-1 virions, while HSV-2 glycoproteins can be present on the infected cell surface. Since HVEM-gD interaction together with gB/gH/gL is essential for HSV-2 entry, HVEM-bearing HIV-1 (HIV-1/HVEM) may enter HSV-2-infected cells through such interactions. To test this hypothesis, we first confirmed the presence of HVEM on HIV-1 virions and glycoproteins on the HSV-2-infected cell surface. Additional studies showed that HIV-1/HVEM bound to the HSV-2-infected cell surface in an HSV-2 infection-time-dependent manner via HVEM-gD interaction. HIV-1/HVEM entry of HSV-2-infected cells was dependent on HVEM-gD interaction and the presence of gB/gH/gL, and was inhibited by azidothymidine. Furthermore, peripheral blood mononuclear cell-derived HIV-1 infected HSV-2-infected primary foreskin epithelial cells and the infection was inhibited by anti-HVEM/gD antibodies. Together, our results indicate that HIV-1 produced from CD4+ T cells bears HSV-2 receptor HVEM and can bind to and enter HSV-2-infected epithelial cells depending on HVEM-gD interaction and the presence of gB/gH/gL. Our findings provide a potential new mechanism underlying HSV-2 infection-enhanced HIV-1 mucosal transmission and may shed light on HIV-1 prevention.

Item Type: Article
Additional Information: This is the accepted manuscript of an article published in the Journal of General Virology at http://doi.org/10.1099/jgv.0.000895
Keywords: Virology, 06 Biological Sciences, 07 Agricultural And Veterinary Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Gen Virol
ISSN: 1465-2099
Language: eng
Dates:
DateEvent
1 September 2017Published
15 August 2017Published Online
17 July 2017Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
31500146National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81572009National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
201604910184China Scholarship Councilhttp://dx.doi.org/10.13039/501100004543
PubMed ID: 28809154
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/109092
Publisher's version: https://doi.org/10.1099/jgv.0.000895

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