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HIV-1持续存在的表观遗传调控及病毒根除的不断演变策略

Epigenetic regulation of HIV-1 persistence and evolving strategies for virus eradication.

作者信息

Dhamija Neeru, Rawat Pratima, Mitra Debashis

机构信息

National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, Pune, 411007, India.

出版信息

Subcell Biochem. 2013;61:479-505. doi: 10.1007/978-94-007-4525-4_21.

Abstract

Despite the intense effort put by researchers globally to understand Human Immunodeficiency Virus (HIV-1) pathogenesis since its discovery 30 years ago, the acquired knowledge till date is not good enough to eradicate HIV-1 from an infected individual. HIV-1 infects cells of the human immune system and integrates into the host cell genome thereby leading to persistent infection in these cells. Based on the activation status of the cells, the infection could be productive or result in latent infection. The current regimen used to treat HIV-1 infection in an AIDS patient includes combination of antiretroviral drugs called Highly Active Anti-Retroviral Therapy (HAART). A major challenge for the success of HAART has been these latent reservoirs of HIV which remain hidden and pose major hurdle for the eradication of virus. Combination of HAART therapy with simultaneous activation of latent reservoirs of HIV-1 seems to be the future of anti-retroviral therapy; however, this will require a much better understanding of the mechanisms and regulation of HIV-1 latency. In this chapter, we have tried to elaborate on HIV-1 latency, highlighting the strategies employed by the virus to ensure persistence in the host with specific focus on epigenetic regulation of latency. A complete understanding of HIV-1 latency will be extremely essential for ultimate eradication of HIV-1 from the human host.

摘要

尽管自30年前发现人类免疫缺陷病毒(HIV-1)以来,全球研究人员付出了巨大努力来了解其发病机制,但迄今为止所获得的知识仍不足以从感染个体中根除HIV-1。HIV-1感染人类免疫系统细胞并整合到宿主细胞基因组中,从而导致这些细胞持续感染。根据细胞的激活状态,感染可能是有生产性的,也可能导致潜伏感染。目前用于治疗艾滋病患者HIV-1感染的方案包括一种名为高效抗逆转录病毒疗法(HAART)的抗逆转录病毒药物组合。HAART成功的一个主要挑战是这些HIV潜伏库,它们仍然隐藏着,对病毒的根除构成了重大障碍。将HAART疗法与同时激活HIV-1潜伏库相结合似乎是抗逆转录病毒疗法的未来;然而,这需要对HIV-1潜伏的机制和调控有更好的理解。在本章中,我们试图详细阐述HIV-1潜伏,突出病毒为确保在宿主中持续存在所采用的策略,并特别关注潜伏的表观遗传调控。对HIV-1潜伏的全面理解对于最终从人类宿主中根除HIV-1极为重要。

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