title: Antimicrobial peptide LL-37 produced by HSV-2-infected keratinocytes enhances HIV infection of Langerhans cells.
abstract: Herpes simplex virus (HSV)-2 shedding is associated with increased risk for sexually acquiring HIV. Because Langerhans cells (LCs), the mucosal epithelium resident dendritic cells, are suspected to be one of the initial target cell types infected by HIV following sexual exposure, we examined whether and how HSV-2 affects HIV infection of LCs. Although relatively few HSV-2/HIV-coinfected LCs were detected, HSV-2 dramatically enhanced the HIV susceptibility of LCs within skin explants. HSV-2 stimulated epithelial cell production of antimicrobial peptides (AMPs), including human β defensins and LL-37. LL-37 strongly upregulated the expression of HIV receptors in monocyte-derived LCs (mLCs), thereby enhancing their HIV susceptibility. Culture supernatants of epithelial cells infected with HSV-2 enhanced HIV susceptibility in mLCs, and this effect was abrogated by blocking LL-37 production. These data suggest that HSV-2 enhances sexual transmission of HIV by increasing HIV susceptibility of LCs via epithelial cell production of LL-37.
authors: Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors: Youichi
authors: Y
authors: Ogawa
authors: Tatsuyoshi
authors: T
authors: Kawamura
authors: Takamitsu
authors: T
authors: Matsuzawa
authors: Rui
authors: R
authors: Aoki
authors: Peter
authors: P
authors: Gee
authors: Atsuya
authors: A
authors: Yamashita
authors: Kohji
authors: K
authors: Moriishi
authors: Kenshi
authors: K
authors: Yamasaki
authors: Yoshio
authors: Y
authors: Koyanagi
authors: Andrew
authors: A
authors: Blauvelt
authors: Shinji
authors: S
authors: Shimada
mesh_terms: D023181:Antimicrobial Cationic Peptides; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D054804:Cathelicidins / Q000378:metabolism*; D015658:HIV Infections / Q000209:etiology / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006561:Herpes Simplex / Q000150:complications* / Q000378:metabolism / Q000821:virology; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000821:virology; D007801:Langerhans Cells / Q000378:metabolism / Q000821:virology*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; D015704:CD4 Antigens; D054804:Cathelicidins; D019713:Receptors, CCR5; D015728:Receptors, HIV