| Project/Area Number |
22390089
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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 |
Virology
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| Research Institution | Kumamoto University |
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Principal Investigator |
UENO Takamasa 熊本大学, エイズ学研究センター, 准教授 (10322314)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Toshiyuki 長崎大学, 熱帯医学研究所, 客員教授 (00296576)
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| Co-Investigator(Renkei-kenkyūsha) |
GATANAGA Hiroyuki 国立国際医療研究センター, エイズ治療・研究開発センター, 治療開発室長 (10466211)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2010: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 感染防御 / ワクチン / ウイルス / 感染症 / 免疫学 / 進化 |
|---|
| Research Abstract |
Impaired HIV-1 Gag, Pol, and Env function has been described inelite controllers (EC) who spontaneously suppress plasma viremia to < 50 RNA copies/mL;however, activity of the accessory protein Nef remains incompletely characterized. Weexamined the ability of 91 Nef sequences, isolated from plasma of 45 EC and 46 chronicprogressors (CP), to down-regulate HLA class I and CD4, up-regulate HLA class II invariantchain (CD74), enhance viral infectivity, and stimulate viral replication in PBMC. Ingeneral, EC Nef sequences were functional; however, all five activities weresignificantly lower in EC compared to CP. Nef from HLA-B*57-expressing EC exhibited poorerCD4 down-regulation function compared to non-B*57 EC, and the number of EC-specificB*57-associated Nef polymorphisms correlated inversely with 4 of 5 Nef functions in theseindividuals. Results indicate that decreased viral protein function, due in part to hostimmune selection pressures, may be a hallmark of the EC phenotype.
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