Herpes simplex virus type 2 enhances HIV-1 susceptibility by affecting Langerhans cell function.
Genital herpes is the most prevalent viral sexually transmitted infection worldwide and is mainly caused by HSV type 2 (HSV-2). HSV-2 infection enhances HIV-1 susceptibility, even in the absence of clinical symptoms. In this study, we investigated the effect of HSV-2 on HIV-1 transmission by mucosal Langerhans cells (LCs). LCs are important in heterosexual transmission because they form a barrier against HIV-1 infection; LCs efficiently capture and degrade HIV-1 through the C-type lectin langerin, thereby preventing HIV-1 transmission. Notably, our data showed that HSV-2 enhanced HIV-1 infection of LCs and subsequent HIV-1 transmission to T cells. HSV-2 interfered with HIV-1 capture by langerin, which allowed efficient HIV-1 infection of LCs. HSV-2 inhibited the antiviral function of langerin at two levels; HSV-2 decreased langerin expression and competed with HIV-1 for langerin binding. HSV-2 replication was not required, because both UV-inactivated HSV-2 and TLR-3 agonist polyinosinic:polycytidylic acid similarly increased HIV-1 transmission by LCs. Therefore, we identified a mechanism by which HSV-2 enhances HIV-1 susceptibility, even in the absence of clinical symptoms. Our data demonstrated that viral coinfections, such as HSV-2, breach the protective function of LCs by abrogating langerin function, which increases HIV-1 susceptibility. These data reinforce the importance of preventing sexually transmitted infections, such as HSV-2, to reduce the transmission of HIV-1.
de Jong
Marein A W P
MA
Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
de Witte
Lot
L
Taylor
Maureen E
ME
Geijtenbeek
Teunis B H
TB
D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D004198:Disease Susceptibility / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000473:pathology / Q000635:transmission; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006558:Herpes Genitalis / Q000150:complications / Q000473:pathology; D018258:Herpesvirus 2, Human / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D012307:Risk Factors; D014771:Virion / Q000378:metabolism; D014775:Virus Activation / Q000276:immunology
D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins