Molecular Virology and Gene Therapy, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Viruses. 2022 Dec 21;15(1):32. doi: 10.3390/v15010032.
To complete their replication cycle, retroviruses need to integrate a DNA copy of their RNA genome into a host chromosome. Integration site selection is not random and is driven by multiple viral and cellular host factors specific to different classes of retroviruses. Today, overwhelming evidence from cell culture, animal experiments and clinical data suggests that integration sites are important for retroviral replication, oncogenesis and/or latency. In this review, we will summarize the increasing knowledge of the mechanisms underlying the integration site selection of the gammaretrovirus MLV and the lentivirus HIV-1. We will discuss how host factors of the integration site selection of retroviruses may steer the development of safer viral vectors for gene therapy. Next, we will discuss how altering the integration site preference of HIV-1 using small molecules could lead to a cure for HIV-1 infection.
为了完成它们的复制周期，逆转录病毒需要将其 RNA 基因组的 DNA 拷贝整合到宿主染色体中。整合位点的选择不是随机的，而是由多种特定于不同逆转录病毒类别的病毒和细胞宿主因素驱动的。如今，来自细胞培养、动物实验和临床数据的压倒性证据表明，整合位点对于逆转录病毒的复制、致癌和/或潜伏至关重要。在这篇综述中，我们将总结关于γ逆转录病毒 MLV 和慢病毒 HIV-1 整合位点选择背后机制的不断增加的知识。我们将讨论逆转录病毒整合位点选择的宿主因素如何引导更安全的基因治疗病毒载体的开发。接下来，我们将讨论如何使用小分子改变 HIV-1 的整合位点偏好，从而可能治愈 HIV-1 感染。
