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靶向与理解HIV潜伏:针对前病毒的CRISPR系统

Targeting and Understanding HIV Latency: The CRISPR System against the Provirus.

作者信息

Magro Gloria, Calistri Arianna, Parolin Cristina

机构信息

Department of Molecular Medicine, Microbiology and Virology Unit, University of Padua, 35121 Padua, Italy.

出版信息

Pathogens. 2021 Sep 28;10(10):1257. doi: 10.3390/pathogens10101257.

Abstract

The presence of latently infected cells and reservoirs in HIV-1 infected patients constitutes a significant obstacle to achieve a definitive cure. Despite the efforts dedicated to solve these issues, the mechanisms underlying viral latency are still under study. Thus, on the one hand, new strategies are needed to elucidate which factors are involved in latency establishment and maintenance. On the other hand, innovative therapeutic approaches aimed at eradicating HIV infection are explored. In this context, advances of the versatile CRISPR-Cas gene editing technology are extremely promising, by providing, among other advantages, the possibility to target the HIV-1 genome once integrated into cellular DNA (provirus) and/or host-specific genes involved in virus infection/latency. This system, up to now, has been employed with success in numerous in vitro and in vivo studies, highlighting its increasing significance in the field. In this review, we focus on the progresses made in the use of different CRISPR-Cas strategies to target the HIV-1 provirus, and we then discuss recent advancements in the use of CRISPR screens to elucidate the role of host-specific factors in viral latency.

摘要

在HIV-1感染患者中,潜伏感染细胞和病毒储存库的存在是实现彻底治愈的重大障碍。尽管致力于解决这些问题,但病毒潜伏的潜在机制仍在研究中。因此,一方面,需要新的策略来阐明哪些因素参与潜伏期的建立和维持。另一方面,正在探索旨在根除HIV感染的创新治疗方法。在这种背景下,多功能CRISPR-Cas基因编辑技术的进展极具前景,它具有诸多优势,包括能够靶向整合到细胞DNA(前病毒)中的HIV-1基因组和/或参与病毒感染/潜伏期的宿主特异性基因。到目前为止,该系统已在众多体外和体内研究中成功应用,凸显了其在该领域日益重要的地位。在这篇综述中,我们重点关注使用不同CRISPR-Cas策略靶向HIV-1前病毒所取得的进展,然后讨论使用CRISPR筛选来阐明宿主特异性因子在病毒潜伏中的作用的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/8539363/3f0caaf405c5/pathogens-10-01257-g001.jpg

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