Ivanovsky Institute of Virology, Gamaleya National Research Center of Epidemiology and Microbiology, Moscow, Russia.
Dokl Biol Sci. 2023 Aug;511(1):251-254. doi: 10.1134/S0012496623700412. Epub 2023 Oct 13.
As a natural mutation of the human ccr5 gene has been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, a new avenue has opened in the development of alternative treatment approaches through genome editing. One of the two chemokine co-receptors of the plasma membrane is utilized by HIV-1 to infect CD4 cells. HIV-1 strains that utilize CCR5 circulate in early infection, and strains that utilize CXCR4 circulate at advanced stages. A complex relationship may exist in the expression regulation of the receptors and may affect virus replication in cells that normally do not express CCR5 on the membrane, such as the MT-4 cell line. MT-4 cells were used to study the effect of ccr5 modification HIV-1 replication in vitro. Genetic modification of ccr5 in MT-4 cells was shown to increase the activities of HIV-1 strains, especially in homozygote. The results indicate that genome editing should be performed with caution in human cells and that the issue needs comprehensive investigation.
作为人类 ccr5 基因的自然突变已被证明可赋予对人类免疫缺陷病毒 1（HIV-1）感染的抗性，因此通过基因组编辑开发替代治疗方法的新途径已经打开。细胞膜的两种趋化因子共受体之一被 HIV-1 用于感染 CD4 细胞。在早期感染中循环利用 CCR5 的 HIV-1 株，在晚期感染中循环利用 CXCR4 的 HIV-1 株。受体的表达调控可能存在复杂的关系，并可能影响通常不在细胞膜上表达 CCR5 的细胞中的病毒复制，例如 MT-4 细胞系。MT-4 细胞被用于研究 ccr5 修饰 HIV-1 复制的体外效果。在 MT-4 细胞中对 ccr5 的基因修饰被证明会增加 HIV-1 株的活性，尤其是在纯合子中。结果表明，在人类细胞中进行基因组编辑时应谨慎操作，并且需要对该问题进行全面调查。
