| Project/Area Number |
23390282
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
SHIMADA Shinji 山梨大学, 医学工学総合研究部, 教授 (10114505)
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| Co-Investigator(Kenkyū-buntansha) |
KKAWAMURA Tatsuyoshi 山梨大学, 医学部附属病院, 講師 (70262657)
SHIBAGAKI Naotaka 山梨大学, 医学工学総合研究部, 准教授 (40262662)
HARADA Kazutoshi 山梨大学, 医学部附属病院, 講師 (20324197)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2011: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
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| Keywords | HSV / HIV / 経皮感染 / ランゲルハンス細胞 / 抗菌ペプチド / 性行為感染症 / 自然免疫 |
|---|
| Research Abstract |
HSV-2 shedding is associated with increased risk for sexually acquiring HIV. Because Langerhans cells (LCs) are suspected to be the initial target cells infected by HIV following sexual exposure, we studied whether HSV-2 affects HIV infection of LCs. HSV-2 enhanced HIV susceptibility in LCs within skin explants, even though relatively few HSV-2/HIV co-infected LCs were detected, suggesting that HSV-2 enhances HIV infection of LCs through indirect mechanisms. Indeed, HSV-2 stimulated production of antimicrobial peptides (AMPs) by epithelial cells, including human defensins and LL-37, and the latter strongly enhanced HIV susceptibility in LCs by up-regulating HIV receptors. Culture supernatants of epithelial cells infected with HSV-2 enhanced HIV susceptibility in LCs, 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.
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