Multifunctional facets of retrovirus integrase

• 作者: Duane P Grandgenett Hideki Aihara Krishan K Pandey Sibes Bera
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: RETROVIRUS INTEGRASE Integration HOST factors Atomic structure Human IMMUNODEFICIENCY virus INTEGRASE inhibitors
• 年，卷（期）: 2015,（3）
• 页码范围: 83-94
• 页数: 12页
• 分类号: R373

摘要

The retrovirus integrase(IN) is responsible for integration of the reverse transcribed linear c DNA into the host DNA genome. First, IN cleaves a dinucleotide from the 3’ OH blunt ends of the viral DNA exposing the highly conserved CA sequence in the recessed ends. IN utilizes the 3’ OH ends to catalyze the concerted integration of the two ends into opposite strands of the cellular DNA producing 4 to 6 bp staggered insertions, depending on the retrovirus species. The staggered ends are repaired by host cell machinery that results in a permanent copy of the viral DNA in the cellular genome. Besides integration, IN performs other functions in the replication cycle of several studied retroviruses. The proper organization of IN within the viral internal core is essential for the correct maturation of the virus. IN plays a major role in reverse transcription by interacting directly with the reverse transcriptase and by binding to the viral capsid protein and a cellular protein. Recruitment of several other host proteins into the viral particle are also promoted by IN. IN assists with the nuclear transport of the preintegration complex across the nuclear membrane. With several retroviruses, IN specifically interacts with different host protein factors that guide the preintegration complex to preferentially integrate the viral genome into specific regions of the host chromosomal target. Human gene therapy using retrovirus vectors is directly affected by the interactions of IN with these host factors. Inhibitors directed against the human immunodeficiency virus(HIV) IN bind within the active site of IN containing viral DNA ends thus preventing integration and subsequent HIV/AIDS.