Understanding HAM pathogenesis through analysis of viral dynamics and immune response in early STLV-1 infection
| Project/Area Number |
19K17049
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Yamauchi Junji 聖マリアンナ医科大学, 医学研究科, 講師 (80760347)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | HAM / HTLV-1 / 免疫抑制薬 / 腎移植 / STLV-1 |
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| Outline of Research at the Start |
ヒトT細胞白血病ウイルス（HTLV-1）は感染者の約0.3%に神経難病であるHTLV-1関連脊髄症（HAM）を引き起こすが、最近我々は、HTLV-1陽性ドナーからの腎移植によって新規に感染したレシピエントは移植後早期に極めて高率（40%）にHAMを発症することを報告した。本研究では、STLV-1（HTLV-1に相同性が高いサルT細胞白血病ウイルス）のサル感染モデルを用いて、感染早期のSTLV-1の動態や宿主免疫応答、またそれらに対する免疫抑制療法および腎移植の影響を解析し、HAM発症機構の理解に繋がるウイルス免疫学的特徴の究明を目指す。
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| Outline of Final Research Achievements |
In order to obtain knowledge that will lead to a better understanding of the pathogenesis of HAM, we analyzed the effects of the unique environment of new HTLV-1 infection in renal transplantation (use of immunosuppressive drugs and presence of a foreign body (another person's kidney)) on virus dynamics and immune responses using a model of HTLV-1 infection in cynomolgus macaques. Interesting changes regarding viral spread and immune response were observed with the use of immunosuppressive drugs. Although the schedule was delayed due to the novel coronavirus pandemic, analysis of the effects of kidney transplantation (plus immunosuppressive drugs) is currently being conducted.
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| Academic Significance and Societal Importance of the Research Achievements |
HAMは、進行性の神経症状を引き起こす稀少難病で、重症例では寝たきりに至り、排尿困難、頑固な便秘、下肢のしびれや痛みなど様々な症状を引き起こす。有効な治療法は確立されておらず、動物モデルがないことが、発症メカニズムの解明や根本治療の開発の大きな障壁となっている。本研究は、HAM動物モデルの確立や発症機構の解明に寄与する可能性がある。
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Health-related quality of life evaluation using the Short Form-36 in patients with human T-cell leukemia virus type 1-associated myelopathy.2022
Author(s)
Kimura M, Yamauchi J, Sato T, Yagishita N, Araya N, Aratani S, Tanabe K, Horibe E, Watanabe T, Coler-Reilly A, Nagasaka M, Akasu Y, Kaburagi K, Kikuchi T, Shibata S, Matsumoto H, Koseki A, Inoue S, Takata A, Yamano Y.
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Journal Title
Front Med
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Efficacy of corticosteroid therapy for HTLV-1-associated myelopathy: A randomized controlled trial (HAMLET-P).2022
Author(s)
Yamauchi J, Tanabe K, Sato T, Nakagawa M, Matsuura E, Tsuboi Y, Tamaki K, Sakima H, Ishihara S, Ohta Y, Matsumoto N, Kono K, Yagishita N, Araya N, Takahashi K, Kunitomo Y, Nagasaka M, Coler-Reilly ALG, Hasegawa Y, Araujo A, Jacobson S, Grassi MFR, Galvao-Castro B, Bland M, Taylor GP, Martin F, Yamano Y.
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Journal Title
Viruses
Volume: in press
Issue: 1
Pages: 136-136
DOI
Related Report
Peer Reviewed
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[Journal Article] Mortality and risk of progression to adult T-cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis.2020
Author(s)
Nagasaka M, Yamagishi M, Yagishita N, Araya N, Kobayashi S, Makiyama J, Kubokawa M, Yamauchi J, Hasegawa D, Coler-Reilly ALG, Tsutsumi S, Uemura Y, Arai A, Takata A, Inoue E, Hasegawa Y, Watanabe T, Suzuki Y, Uchimaru K, Sato T, Yamano Y.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 117(21)
Issue: 21
Pages: 11685-11691
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Risk Factors for Death within 6 Months After Ischemic Stroke in Patients with Cancer.2020
Author(s)
Tsuchihashi Y, Shimizu T, Akiyama H, Hagiwara Y, Soga K, Takao N, Uchino K, Yanagisawa T, Yamauchi J, Sato T, Hasegawa Y, Yamano Y.
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Journal Title
J Stroke Cerebrovasc Dis
Volume: 29(12)
Issue: 12
Pages: 105365-105365
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Creation and validation of a bladder dysfunction symptom score for HTLV-1-associated myelopathy/tropical spastic paraparesis.2020
Author(s)
Yamakawa N, Yagishita N, Matsuo T, Yamauchi J, Ueno T, Inoue E, Takata A, Nagasaka M, Araya N, Hasegawa D, Coler-Reilly A, Tsutsumi S, Sato T, Araujo A, Casseb J, Gotuzzo E, Jacobson S, Martin F, Puccioni-Sohler M, Taylor GP, Yamano Y; Japan Clinical Research Group on HAM/TSP.
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Journal Title
Orphanet J Rare Dis
Volume: 15(1)
Issue: 1
Pages: 175-175
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cerebrospinal Fluid CXCL10 as a Candidate Surrogate Marker for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.2019
Author(s)
Tamaki K, Sato T, Tsugawa J, Fujioka S, Yagishita N, Araya N, Yamauchi J, Coler-Reilly A, Nagasaka M, Hasegawa Y, Yamano Y, Tsuboi Y.
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Journal Title
Front Microbiol
Volume: 10
Pages: 2110-2110
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] リアルワールドデータにより示されたHAMの排尿障害に対するミラベグロンの有用性.2021
Author(s)
飯島直樹, 山内淳司, 髙梨世子, 太刀川慶史, 八木下尚子, 新谷奈津美, 荒谷聡子, 田辺健一郎, 佐藤知雄, 高田礼子, 山野嘉久.
Organizer
第7回日本HTLV-1学会学術集会
Related Report
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