Sojane Katlego, Kangethe Richard T, Chang Christina C, Moosa Mahomed-Yunus S, Lewin Sharon R, French Martyn A, Ndung'u Thumbi
1 HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal , Durban, South Africa .
2 Department of Infectious Diseases, Alfred Hospital and Monash University , Melbourne, Australia .
AIDS Res Hum Retroviruses. 2018 Jul;34(7):607-620. doi: 10.1089/AID.2017.0209. Epub 2018 May 23.
The genotypic properties of human immunodeficiency virus type 1 (HIV-1) subtype C in individuals presenting with cryptococcal meningitis (CM) are not well established. Employing single-genome amplification as well as bulk PCR, cloning and sequencing strategies, we evaluated the genetic properties of HIV-1 subtype C env in 16 antiretroviral therapy-naive study participants with CM. Eleven of the 16 participants had matched blood plasma and cerebrospinal fluid (CSF) evaluated, with the rest having either a plasma or CSF sample evaluated. Before antiretroviral therapy initiation, matched plasma and CSF-derived env sequences of all 11 participants displayed genetic intermixing between the two compartments. Overall, 7 of the 16 (∼43.8%) participants harbored CXCR4-using variants in plasma and/or CSF, according to coreceptor usage prediction algorithms. This study suggests that HIV-1 subtype C genetic intermixing between peripheral blood and the central nervous system is common in individuals presenting with CM, and that CXCR4 usage is present in one or both compartments in approximately 44% of individuals.
1型人类免疫缺陷病毒（HIV-1）C亚型在隐球菌性脑膜炎（CM）患者中的基因型特性尚未完全明确。我们采用单基因组扩增以及大量聚合酶链反应（PCR）、克隆和测序策略，评估了16例初治抗逆转录病毒治疗的CM研究参与者中HIV-1 C亚型env基因的特性。16名参与者中有11名同时评估了匹配的血浆和脑脊液（CSF），其余参与者仅评估了血浆或CSF样本。在开始抗逆转录病毒治疗之前，所有11名参与者匹配的血浆和CSF来源的env序列在两个区室之间呈现基因混合。总体而言，根据共受体使用预测算法，16名参与者中有7名（约43.8%）在血浆和/或CSF中携带使用CXCR4的变异体。本研究表明，在CM患者中，外周血和中枢神经系统之间的HIV-1 C亚型基因混合很常见，并且在约44%的个体中，一个或两个区室中存在CXCR4的使用情况。
