Detection of primary target cells for HIV-1 in skin explant model and the functional role of HIV infected DC

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390338
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Yamanashi
• Principal Investigator: KAWAMURA Tatsuyoshi University of Yamanashi, University of Yamanashi Hospital, Lecturer, 医学部附属病院, 講師 (70262657)
• Project Period (FY): 2003 – 2004
• Keywords: Langerhans cell / HIV / Skin explant model / CCR5 / c-type lectin receptor / DC-SIGN / Langerin

Research Abstract

We studied relevant host molecular targets utilized for acquisition of HIV infection using a skin explant model system. HIV_<BaL> was applied to the abraded epidermal surface of skin explants. After 3 days, emigrant cells from skin explants were co-cultured with allogeneic T cells. HIV p24 levels in culture supernatants were monitored by ELISA. Interestingly, preincubation of skin explants with PSC-RANTES completely blocked subsequent HIV transmission from emigrant cells to T cells, whereas mannan did not. Strikingly, when infection levels of single LC or DC within emigrant cells were determined, HIV p24+ cells were detected only in LC, but not in DC. To test whether HIV could replicate within LC, skin explants were exposed to HIV variants that were engineered to express GFP during productive infection of cells. HLA-DR+/ Langerin+/ GFP+ emigrated cells were detected in LC-T cell conjugates, when a CCR5-using HIV isolate, but not a CXCR4-using HIV isolate, was applied to skin. Thus, CCR5-mediated productive HIV infection of LC, and not C-type lectin-mediated capture of virus by DC, may provide a biologic basis for understanding susceptibility to initial infection by CCR5-using strains of HIV in humans.