2013 Fiscal Year Final Research Report
The elucidation of the early immune system in percutaneous infection of HSV and HIV and the development of novel methods to prevent their cutaneous infection
| 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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| Keywords | HSV / HIV / 経皮感染 / ランゲルハンス細胞 / 抗菌ペプチド |
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| 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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Research Products
(13 results)
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[Journal Article] Case of primary cutaneous peripheral T-cell lymphoma, not otherwise specified, with characteristics of follicular helper T cells2014
Author(s)
Takaki M, Inozume T, Matsuzawa T, Ando N, Y amaguchi M, Harada K, Kawamura T, Shibagaki N, Shimada S
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Journal Title
J Dermatol
Volume: (In press)
DOI
Peer Reviewed
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[Journal Article] EFdA, a reverse transcriptase inhibitor , potently blocks HIV -1 ex vivo infection of Langerhans cells within epithelium2014
Author(s)
Matsuzawa T, Kawamura T, Ogawa Y, Maeda K, Nakata H, Moriishi K, Koyanagi Y, Gatanaga H, Shimada S, Mitsuya H
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Journal Title
J Invest Dermatol
Volume: 134(4)
Pages: 1158-61
DOI
Peer Reviewed
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[Journal Article] Oral administration of the CCR5 inhibitor , maraviroc, blocks HIV ex vivo infection of Langerhans cells within the epithelium2013
Author(s)
Matsuzawa T, Kawamura T, Ogawa Y, Takahashi M, Aoki R, Moriishi K, Koyanagi Y, Gatanaga H, Blauvelt A, Shimada S
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Journal Title
J Invest Dermatol
Volume: 133(12)
Pages: 2803-5
DOI
Peer Reviewed
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[Journal Article] Antimicrobial peptide LL-37 produced by HSV -2-infected keratinocytes enhances HIV infection of Langerhans cells2013
Author(s)
Ogawa Y, Kawamura T, Matsuzawa T, Aoki R, Gee P, Y amashita A, Moriishi K, Y amasaki K, Koyanagi Y, Blauvelt A, Shimada S
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Journal Title
Cell Host Microbe
Volume: 16;13(1)
Pages: 77-86
DOI
Peer Reviewed
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[Journal Article] Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency2012
Author(s)
Kawamura T, Ogawa Y, Nakamura Y, Nakamizo S, Ohta Y, Nakano H, Kabashima K, Katayama I, Koizumi S, Kodama T, Nakao A, Shimada S
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Journal Title
J Clin Invest
Volume: 122(2)
Pages: 722-32
DOI
Peer Reviewed
