| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Even under highly active anti-retroviral therapy using extensive combination of inhibitors to reverse transcriptase and/or protease, eradication of human immunodeficiency virus (HIV) remains to be achieved. Thus, development of new inhibitors that block new targets as well as reverse transcriptase or protease is urgently required. In this project, the principal investigator focuses on a viral accessory protein, Rev that is essential for HIV replication and has developed peptide based Rev inhibitors.
The investigator found that a peptide containing 10 to 63 amino acids of Rev transduced cells were resistant to HIV infection, suggesting that the region contains an HIV inhibitory peptide sequence. To identify the region, expression vectors containing peptide sequences in various size and region of Rev 10 to 63 were constructed. Among them, a peptide containing arginine rich 34 to 50 amino acid sequence showed inhibitory effect. Addition of four alanines that stabilize α-helical structure enhances the inhibitory effect. Human T-cell leukemia virus Rex, a homolog of Rev also has arginine rich domain. This region also showed inhibitory effect to HIV infection. Synthetic peptides also block HIV infections through its binding to CXCR4, not through suppression of Rev function, indicating that enhancement of peptide penetration efficiency into cells is needed. Further study is needed to develop clinically useful Rev inhibitors.
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