| Project/Area Number |
14570268
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of the Ryukyus |
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Principal Investigator |
MURAKAMI Tsutomu University of the Ryukyus, Graduate School of Medicine, Associate Professor, 医学部, 助教授 (50336385)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Atsushi University of the Ryukyus, Graduate School of Medicine, Assistant Professor, 医学部, 助手 (10242778)
TANAKA Yuetsu University of the Ryukyus, Graduate School of Medicine, Professor, 医学部, 教授 (30163588)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | HIV-1 / Env proteins / Gag proteins / Virus binding / entry / Membrane fusion / Processing / Viral protease / プロテアーゼ |
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| Research Abstract |
We and others have presented evidence for a direct interaction between the matrix(MA) domain of the human immunodeficiency virus type 1(HIV-1) Gag protein and the cytoplasmic tail of the transmembrane envelope(Env) glycoprotein gp41. In addition, it has been postulated that the MA domain of Gag undergoes a conformational change following Gag processing and the cytoplasmic tail of gp41 has been shown to modulate Env-mediated membrane fusion activity. Together, these results raise the possibility that the interaction between the gp41 cytoplasmic tail and MA is regulated by protease(PR)-mediated Gag processing, perhaps affecting Env function. To examine whether Gag processing affects Env-mediated fusion, we compared the ability of WT HIV-1 Env and a mutant lacking the gp41 cytoplasmic tail to induce fusion in the context of an active(PR^+) or inactive(PR^-) viral PR. We observed that PR^-virions bearing WT Env displayed defects in cell-cell fusion. Impaired fusion did not pear to be due to differences in the levels of virion-associated Env, in CD4-dependent binding to target cells, or in the formation of the CD4-induced gp41 six-helix bundle. Interestingly, truncation of the gp41 cytoplasmic tail reversed the fusion defect. These results suggest that interactions between unprocessed Gag and the gp41 cytoplasmic tail suppress fusion.
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