ヒト細胞のDNA損傷によってヒト免疫不全ウイルス1型の活性化
1Department of Molecular Genetics, Smith Kline and French Laboratories, King of Prussia, Pennsylvania 19406-0939.
Nature
|May 5, 1988
まとめ
細胞のストレス反応は,UV光からのものと同様に,ヒト免疫不全ウイルス1型 (HIV) の遺伝子発現とウイルスの複製を大幅に強化します. DNAを損傷する物質は,潜伏したHIV感染を活性化させることができる.
科学分野:
- ウイルス学 ウイルス学 ウイルス学
- 分子生物学は分子生物学である.
- 免疫学 免疫学とは
背景:
- 特定の薬剤は,ヒト免疫不全ウイルス1型 (HIV) の遺伝子発現を高めることができます.
- これらの薬剤は,しばしば細胞のストレス反応を誘発します.
- 細胞のストレス反応は,潜伏しているHIV感染を活性化させる役割を果たす可能性があります.
研究 の 目的:
- HIV遺伝子発現とウイルスの複製に対する細胞ストレス反応の影響を調査する.
- 紫外線やミトミシンCなどのストレスを引き起こす物質がHIV遺伝子発現を高めることができるかどうかを判断する.
主な方法:
- ヒトT細胞におけるHIV遺伝子発現に対する紫外線とミトミシンCの影響を調査した.
- 紫外線照射後のウイルスの成長と発達を評価した.
- UV誘発のHIV遺伝子発現強化の基礎となる分子機構を分析した.
主要な成果:
- 紫外線とミトミシンCは,HIV遺伝子発現を150倍まで増強し,タット遺伝子製品と同等である.
- 紫外線による増強は転写を必要とするが,新しいタンパク質合成は不要であり,安定したmRNAの蓄積と相関する.
- 感染前の紫外線照射は,HIVウイルスの成長サイクルを大幅に短縮しました.
- また,直接の太陽光がHIV遺伝子発現を活性化することが判明しました.
結論:
- 紫外線によって引き起こされる細胞ストレスがHIVの複製と成長を促します.
- DNAを損傷する物質や,SOSのようなストレス反応を誘発する他の物質は,HIVの発現を活性化させることができる.
- これらの発見は,ストレス誘発剤が潜伏したHIV感染を再活性化し,ウイルス発達の可能性を強調しています.
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