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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

Research Project

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Project/Area Number 23390282
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionUniversity of Yamanashi

Principal Investigator

SHIMADA Shinji  山梨大学, 医学工学総合研究部, 教授 (10114505)

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)
Project Period (FY) 2011-04-01 – 2014-03-31
KeywordsHSV / HIV / 経皮感染 / ランゲルハンス細胞 / 抗菌ペプチド
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.

  • Research Products

    (13 results)

All 2014 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 13 results)

  • [Journal Article] A case of oral mucosal fixed eruption caused by methacrylate2014

    • Author(s)
      Inozume T, Nakazawa R, Tanaka K, Harada K, Kawamura T, Shibagaki N, Shimada S
    • Journal Title

      Contact Dermatitis

      Volume: 70(6) Pages: 387-8

    • DOI

      10.1111/cod.12183

    • Peer Reviewed
  • [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
    • Journal Title

      J Dermatol

      Volume: (In press)

    • DOI

      10.1111/1346-8138.12493

    • Peer Reviewed
  • [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
    • Journal Title

      J Invest Dermatol

      Volume: 134(4) Pages: 1158-61

    • DOI

      10.1038/jid.2013.467

    • Peer Reviewed
  • [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
    • Journal Title

      J Invest Dermatol

      Volume: 133(12) Pages: 2803-5

    • DOI

      10.1038/jid.2013.215

    • Peer Reviewed
  • [Journal Article] Two cases of autosomal recessive woolly hair with LIPH gene mutations2013

    • Author(s)
      Harada K, Inozume T, Kawamura T, Shibagaki N, Kinoshita T, Deguchi N, Shimada S
    • Journal Title

      Int J Dermatol

      Volume: 52(5) Pages: 572-4

    • DOI

      10.1111/j.1365-4632

    • Peer Reviewed
  • [Journal Article] Mast cells play a key role in host defense against herpes simplex virus infection through TNF-α and IL-6 production2013

    • Author(s)
      Aoki R, Kawamura T, Goshima F, Ogawa Y, Nakae S, Nakao A, Moriishi K, Nishiyama Y, Shimada S
    • Journal Title

      J Invest Dermatol

      Volume: 133(9) Pages: 2170-9

    • DOI

      10.1038/jid.2013.150

    • Peer Reviewed
  • [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
    • Journal Title

      Cell Host Microbe

      Volume: 16;13(1) Pages: 77-86

    • DOI

      10.1016/j.chom.2012.12.002

    • Peer Reviewed
  • [Journal Article] A case of dermatomyositis accompanied by spontaneous intramuscular hemorrhage despite normal coagulability2013

    • Author(s)
      Hanawa F, Inozume T, Harada K, Andou N, Kawamura T, Shibagaki N, Shimada S
    • Journal Title

      Rheumatol Int

      Volume: 33(11) Pages: 2949-50

    • DOI

      10.1007/s00296-012-2492-3

    • Peer Reviewed
  • [Journal Article] Case of rheumatoid papules : is this a link between vasculitis and rheumatoid nodules?2012

    • Author(s)
      Inozume T, Ando N, Sano S, Harada K, Kawamura T, Shibagaki N, Shimada S
    • Journal Title

      J Dermatol

      Volume: 39(12) Pages: 1091-2

    • DOI

      10.1111/j.1346-8138.2012.01597

    • Peer Reviewed
  • [Journal Article] Neutrophilic panniculitis with non-caseating granulomas in a Crohn's disease patient2012

    • Author(s)
      Ogawa Y, Aoki R, Harada K, Matsuzawa T, Inozume T, Shibagaki N, Kawamura T, Shimada S
    • Journal Title

      Eur J Dermatol

      Volume: 22(3) Pages: 404-5

    • DOI

      10.1684/ejd.2012.1737

    • Peer Reviewed
  • [Journal Article] Gutter method : noninvasive management of ingrown nails caused by epidermal growth factor inhibitor treatment2012

    • Author(s)
      Harada K, Y amaguchi M, Miyajima S, Kawamura T, Shibagaki S, Shimada S
    • Journal Title

      Clin Exp Dermatol

      Volume: 37(6) Pages: 703-4

    • DOI

      10.1111/j.1365-2230.2012.04358

    • Peer Reviewed
  • [Journal Article] Case of mucous membrane pemphigoid characterized by circulating immunoglobulin A and immunoglobulin G autoantibodies to the gamma-2 subunit of laminin-3322012

    • Author(s)
      Hanawa F, Harada K, Andou N, Kawamura T, Shibagaki N, Fukuda S, Hashimoto T, Shimada S
    • Journal Title

      J Dermatol

      Volume: 39(11) Pages: 962-3

    • DOI

      10.1111/j.1346-8138.2011.01501

    • Peer Reviewed
  • [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
    • Journal Title

      J Clin Invest

      Volume: 122(2) Pages: 722-32

    • DOI

      10.1172/JCI58618

    • Peer Reviewed

URL: 

Published: 2015-06-25  

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