Pathogenesis of HIV-associated pulmonary hypertension: potential role of HIV-1 Nef.
Pathogenesis of HIV-associated pulmonary hypertension: potential role of HIV-1 Nef.
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DOI：
10.1513/pats.201006-046wr
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Flores, Sonia C
中科院分区：
文献类型：
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作者：
Almodovar, Sharilyn;Hsue, Priscilla Y;Flores, Sonia C
感染HIV会增加肺部疾病的风险，包括非感染性肺动脉高压（PH）。HIV相关PH（HIV-PH）是HIV感染者的一种重要肺部疾病，使用抗逆转录病毒药物可延长其寿命。HIV-PH的早期阶段可能由于非特异性症状而被医疗保健提供者忽视，包括进行性呼吸困难和干咳。HIV-PH可以通过胸片、CT扫描或心电图检测，但多普勒超声心动图是最有用的筛选测试，以确定右心导管插入术的候选人。HIV-PH预后差，死亡率高;改善生物标志物以识别PH的早期阶段将有益于临床护理。HIV-PH机制尚不清楚，但HIV蛋白如达特和Nef可能起作用。HIV-1 Nef是一种广谱衔接蛋白，可影响HIV感染和未感染的肺血管细胞。对猕猴的研究表明，Nef在HIV-PH发病机制中很重要，因为感染了表达HIV-nef（SHIVnef）等位基因的嵌合猴免疫缺陷病毒（SIV）的猴子，而不是感染了天然SIV的猴子，会发生肺血管重塑。在猴中传代的Nef中自发地出现了四个一致的氨基酸突变。为了将这些发现转化为人类，肺HIV研究的一项研究工作集中在与HIV感染的血压正常患者相比，HIV感染的PH患者中HIV nef突变的鉴定。我们提供了一些初步证据。正在进行的纵向研究将建立Nef突变与HIV-PH倾向之间的联系。
Infection with HIV increases the risk for lung diseases, including noninfectious pulmonary hypertension (PH). HIV-associated PH (HIV-PH) is an important lung disease in HIV-infected persons who live longer with antiretrovirals. The early stages of HIV-PH may be overlooked by healthcare providers due to nonspecific symptoms, including progressive dyspnea and nonproductive cough. HIV-PH may be detected via chest radiographs, CT scans, or electrocardiograms, but Doppler echocardiography is the most useful screening test to identify candidates for right heart catheterization. HIV-PH has a poor prognosis with high mortality; improved biomarkers to identify earlier stages of PH would benefit clinical care. The HIV-PH mechanism remains unknown, but HIV proteins such as Tat and Nef may play a role. HIV-1 Nef is a broad-spectrum adaptor protein that may affect HIV-infected and uninfected pulmonary vascular cells. Studies in macaques suggest that Nef is important in HIV-PH pathogenesis because monkeys infected with a chimeric simian immunodeficiency virus (SIV) expressing HIV-nef (SHIVnef) alleles, but not monkeys infected with the native SIV, develop pulmonary vascular remodeling. Four consistent amino acid mutations arose spontaneously in Nef passaged in the monkeys. To translate these findings to humans, one research endeavor of the Lung HIV Study focuses on the identification of HIV nef mutations in HIV-infected individuals with PH compared with HIV-infected normotensive patients. We present some of the preliminary evidence. Ongoing longitudinal studies will establish the connection between Nef mutations and the propensity for HIV-PH.