Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Microbiol Spectr. 2022 Oct 26;10(5):e0254522. doi: 10.1128/spectrum.02545-22. Epub 2022 Oct 10.
HIV-1 CRF07_BC originated among injection drug users (IDUs) in China. After diffusing into men who have sex with men (MSM), CRF07_BC has shown a rapid expansion in this group; however, the mechanism remains unclear. Here, we identified a new KE variant of CRF07_BC that was characterized by five specific mutations (E28K, K32E, E248V, K249Q, and T338S) in reverse transcriptase. This variant was mainly prevalent among MSM, and was overrepresented in transmission clusters, suggesting that it could have driven the rapid expansion of CRF07_BC in MSM, though founder effects cannot be ruled out. It was descended from an evolutionary intermediate accumulating four specific mutations and formed an independent phylogenetic node with an estimated origin time in 2003. The KE variant was demonstrated to have significantly higher HIV-1 replication ability than the wild type. Mutations E28K and K32E play a critical role in the improvement of HIV-1 replication ability, reflected by improved reverse transcription activity. The results could allow public health officials to use this marker (especially E28K and K32E mutations in the reverse transcriptase (RT) coding region) to target prevention measures prioritizing MSM population and persons infected with this variant for test and treat initiatives. HIV-1 has very high mutation rate that is correlated with the survival and adaption of the virus. The variants with higher transmissibility may be more selective advantage than the strains with higher virulence. Several HIV-1 variants were previously demonstrated to be correlated with higher viral load and lower CD4 T cell count. Here, we first identified a new variant (the KE variant) of HIV-1 CRF07_BC, described its origin and evolutionary dynamics, and demonstrated its higher HIV-1 replication ability than the wild type. We demonstrated that five RT mutations (especially E28K and K32E) significantly improve HIV-1 replication ability. The appearance of the new KE variant was associated with the rapidly increasing prevalence of CRF07_BC among MSM.
HIV-1 CRF07_BC 起源于中国的注射吸毒者（IDUs）。在扩散到男男性行为者（MSM）之后，CRF07_BC 在该群体中迅速扩张；然而，其机制尚不清楚。在这里，我们鉴定了 HIV-1 CRF07_BC 的一种新 KE 变异体，其特征在于逆转录酶中有五个特定突变（E28K、K32E、E248V、K249Q 和 T338S）。这种变异体主要在 MSM 中流行，并且在传播群集中占优势，表明它可能是 CRF07_BC 在 MSM 中迅速扩张的驱动因素，尽管不能排除创始效应。它是从一个积累了四个特定突变的进化中间体进化而来的，并形成了一个独立的进化枝，估计起源时间在 2003 年。KE 变异体表现出比野生型更高的 HIV-1 复制能力。突变 E28K 和 K32E 在提高 HIV-1 复制能力方面起着关键作用，这反映在逆转录活性的提高上。这些结果可以使公共卫生官员利用这个标志物（特别是逆转录酶（RT）编码区的 E28K 和 K32E 突变），针对 MSM 人群和感染这种变异体的人群，将预防措施作为重点，以进行检测和治疗。HIV-1 具有非常高的突变率，这与病毒的生存和适应有关。具有更高传播能力的变异体可能比具有更高毒力的菌株具有更大的选择优势。以前已经证明了几种 HIV-1 变异体与更高的病毒载量和更低的 CD4 T 细胞计数相关。在这里，我们首次鉴定了 HIV-1 CRF07_BC 的一种新变异体（KE 变异体），描述了其起源和进化动态，并证明了其比野生型更高的 HIV-1 复制能力。我们证明了五个 RT 突变（特别是 E28K 和 K32E）显著提高了 HIV-1 复制能力。新的 KE 变异体的出现与 CRF07_BC 在 MSM 中迅速增加的流行率有关。
