Antimicrobial Peptide LL-37 Produced by HSV-2-Infected Keratinocytes Enhances HIV Infection of Langerhans Cells

Youichi Ogawa et al. Cell Host Microbe. (2013) 13, 77–86.

Speaker: Yi-Pin Tsai (蔡佾頻)                                       Time: 14:00~15:00, Sep. 25, 2013

Commentator: Shainn-Wei Wang (王憲威 老師)        place: Room 601

Abstract:

Epidemiologic studies have indicated that herpes simplex virus 2 (HSV-2) shedding is associated with increased risk for sexual transmission of human immunodeficiency virus (HIV). During sexual transmission of HIV, virus crosses mucosal epithelium and infects langerhans cells (LCs) which are one of the HIV initial targets. HIV-infected LCs readily emigrate from tissue to draining lymph nodes, where virus can be transmitted to CD4⁺ T cells. In this study, the authors examined how HSV-2 enhanced the acquisition of HIV. First, they found that preincubation of epidermal sheets with HSV-2 significantly increased the percentage of HIV-infected LCs, but the percentage of HSV-2/HIV coinfected-LCs was low. Similarly, culture supernatants from HSV-2-treated keratinocytes also significantly increased the percentage of HIV-infected LCs. Therefore, these results indicated that HSV-2-treated keratinocytes released a soluble factor to enhance HIV infection. It has been shown that human keratinocytes can produce antimicrobial peptides such as defensins and LL-37 which is a human sole cathelicidin, and these peptides can modulate HIV infectivity in CD4⁺ T cells and peripheral blood mononuclear cells. The authors futher found that HSV-2-treated keratinocytes produced LL-37 protein to enhance HIV susceptibility of LCs. Moreover, LL-37 significantly elevated the expression of surface CD4 and CCR5 on LCs which specifically promoted R5 HIV infection. Pretreatment of LCs with LL-37 also significantly increased HIV transmission to CD4⁺ T cells. In conclusion, HSV-2-infected keratinocytes released LL-37 to enhance HIV infection of LCs by upregulating CD4 and CCR5 on the surface of LCs.

References:

1.          The role of Langerhans cells in the sexual transmission of HIV. J. Dermatol. Sci. (2005) 40,147–155.

2.          Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: implications for HIV primary infection. Nat. Med. (1997) 3, 1369–1375.