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Viral protein R polymorphisms in the pathogenesis of HIV-associated acute ischaemic stroke: a case–control study
Journal of Neurovirology ( IF 2.3 ) Pub Date : 2021-01-18 , DOI: 10.1007/s13365-020-00936-y
Kate McMullen 1 , Kathleen Bateman 1 , Alan Stanley 1 , Marc Combrinck 2 , Susan Engelbrecht 3 , Alan Bryer 1
Affiliation  

HIV-1 viral proteins have been implicated in endothelial dysfunction, which is a major determinant of ischaemic stroke risk in HIV-infected individuals. Polymorphisms in HIV-1 viral protein R (Vpr) may alter its potential to promote endothelial dysfunction, by modifying its effects on viral replication, reactivation of latent cells, upregulation of pro-inflammatory cytokines and infection of macrophages. We analysed Vpr polymorphisms and their association with acute ischaemic stroke by comparing Vpr signature amino acids between 54 HIV-infected individuals with acute ischaemic stroke, and 80 age-matched HIV-infected non-stroke controls. Isoleucine at position 22 and serine at position 41 were associated with ischaemic stroke in HIV. Individuals with stroke had lower CD4 counts and CD4 nadirs than controls. These polymorphisms are unique to individuals with stroke compared to South African subtype C and the control group consensus sequences. Signature Vpr polymorphisms are associated with acute ischaemic stroke in HIV. These may increase stroke risk by promoting endothelial dysfunction and susceptibility to opportunistic infections. Therapeutic targeting of HIV-1 viral proteins may present an additional mechanism of decreasing stroke risk in HIV-infected individuals.



中文翻译:

HIV相关急性缺血性卒中发病机制中的病毒蛋白R多态性:病例对照研究

HIV-1 病毒蛋白与内皮功能障碍有关,内皮功能障碍是 HIV 感染者缺血性中风风险的主要决定因素。HIV-1 病毒蛋白 R (Vpr) 的多态性可能会改变其对病毒复制、潜伏细胞再激活、促炎细胞因子上调和巨噬细胞感染的影响,从而改变其促进内皮功能障碍的潜力。我们通过比较 54 名感染 HIV 的急性缺血性中风个体和 80 名年龄匹配的 HIV 感染非中风对照之间的 Vpr 特征氨基酸,分析了 Vpr 多态性及其与急性缺血性中风的关联。22 位异亮氨酸和 41 位丝氨酸与 HIV 缺血性中风有关。与对照组相比,中风个体的 CD4 计数和 CD4 最低点较低与南非 C 亚型和对照组共有序列相比,这些多态性是中风个体所独有的。特征 Vpr 多态性与 HIV 急性缺血性中风有关。这些可能通过促进内皮功能障碍和对机会性感染的易感性来增加中风风险。HIV-1 病毒蛋白的治疗靶向可能是降低 HIV 感染者中风风险的另一种机制。

更新日期:2021-01-19
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