Genomic Characteristics of the New HIV-1 CRF07_BC K28E32 Variant.

IF 1.5 4区 医学 Q4 IMMUNOLOGY AIDS research and human retroviruses Pub Date : 2024-01-01 Epub Date: 2023-07-05 DOI:10.1089/AID.2022.0182
Yingying Ma, Zhenzhou Wan, Min Zhang, Chiyu Zhang
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Abstract

Accompanied with the appearance and prevalence of the new K28E32 variant among men who have sex with men, HIV-1 circulating recombinant form 07_BC (CRF07_BC) was becoming the most predominant subtype circulating in China. The K28E32 variant with five specific mutations in reverse transcriptase coding region appears to have significantly higher in vitro HIV-1 replication ability than the wild-type strain. In this study, we characterized the special mutations/substitutions in the K28E32 variant at the genomic level. Ten specific mutations that rarely appeared in other six main HIV-1 subtypes/CRFs (A-D, CRF01_AE, and CRF02_AG) were identified in the coding genes/regions of the K28E32 variant, including S77L and a novel seven-amino acid detection (32DKELYPL38) (p6Δ7) in p6, I135L in integrase, T189S in Vif, H/Y15L/F in Vpr, I264V/A and LV/LI328-329VG in gp41, and H82C and S97P in Rev. The special locations of the novel p6Δ7, and gp41 mutations I264V/A and LV/LI328-329VG in crucial protein functional domains suggest that these mutations might be functionally important to the K28E32 variant. Furthermore, eight specific substitutions were identified in Rev responsive element (RRE) of the K28E32 variant, and were revealed to increase the stability of RRE structure with a lower minimum free energy. Whether these mutations/substitutions contribute to improved transmissibility of the CRF07_BC K28E32 variant needs to be further confirmed.

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新型 HIV-1 CRF07_BC K28E32 变体的基因组特征
随着新的K28E32变异株在男男性行为人群中的出现和流行,HIV-1循环重组型07_BC(CRF07_BC)正在成为中国最主要的循环亚型。K28E32变异株在逆转录酶编码区发生了五个特异性突变,体外复制HIV-1的能力明显高于野生型株。在本研究中,我们从基因组水平对K28E32变异株中的特殊突变/替换进行了鉴定。我们在 K28E32 变异株的编码基因/区域中发现了 10 个在其他 6 个主要 HIV-1 亚型/CRF(A-D、CRF01_AE 和 CRF02_AG)中很少出现的特殊突变、包括 p6 中的 S77L 和一个新的七氨基酸检测(32DKELYPL38)(p6Δ7)、整合酶中的 I135L、Vif 中的 T189S、Vpr 中的 H/Y15L/F、gp41 中的 I264V/A 和 LV/LI328-329VG 以及 Rev 中的 H82C 和 S97P。新型 p6Δ7 突变和 gp41 突变 I264V/A 和 LV/LI328-329VG 在关键蛋白功能域的特殊位置表明,这些突变可能对 K28E32 变体具有重要功能。此外,还在 K28E32 变体的 Rev 反应元件(RRE)中发现了 8 个特定的取代,结果表明这些取代提高了 RRE 结构的稳定性,降低了最小自由能。这些突变/替换是否有助于提高 CRF07_BC K28E32 变体的可传播性还有待进一步证实。
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来源期刊
CiteScore
3.10
自引率
6.70%
发文量
201
审稿时长
3-6 weeks
期刊介绍: AIDS Research and Human Retroviruses was the very first AIDS publication in the field over 30 years ago, and today it is still the critical resource advancing research in retroviruses, including AIDS. The Journal provides the broadest coverage from molecular biology to clinical studies and outcomes research, focusing on developments in prevention science, novel therapeutics, and immune-restorative approaches. Cutting-edge papers on the latest progress and research advances through clinical trials and examination of targeted antiretroviral agents lead to improvements in translational medicine for optimal treatment outcomes. AIDS Research and Human Retroviruses coverage includes: HIV cure research HIV prevention science - Vaccine research - Systemic and Topical PreP Molecular and cell biology of HIV and SIV Developments in HIV pathogenesis and comorbidities Molecular biology, immunology, and epidemiology of HTLV Pharmacology of HIV therapy Social and behavioral science Rapid publication of emerging sequence information.
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