Suh Andrew J, Suzuki Dante I, Gychka Sergiy G, Brelidze Tinatin I, Suzuki Yuichiro J
bioRxiv. 2023 Jan 3:2023.01.03.522636. doi: 10.1101/2023.01.03.522636.
Cardiovascular complications are seen among human immunodeficiency virus (HIV)-positive individuals who can now survive longer due to successful antiretroviral therapies. Among them, pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased blood pressure in the lung circulation due to vasoconstriction and vascular wall remodeling, resulting in the overworking of the heart. The prevalence of PAH in the HIVpositive population is dramatically higher than that in the general population. While HIV-1 Group M Subtype B is the most prevalent subtype in western countries, the majority of HIV-1 infections in eastern Africa and former Soviet Union countries are caused by Subtype A. Research on the mechanism of vascular complications in the HIV-positive population, especially in the context of subtype differences, however, has not been rigorous. Much of the research on HIV has focused on Subtype B and information on the molecular mechanisms of Subtype A is non-existent. The lack of such knowledge results in health disparities in the development of therapeutic strategies to prevent/treat HIV complications. The present study examined the effects of HIV-1 viral fusion protein gp120 of Subtypes A and B on cultured human pulmonary artery endothelial cells by performing protein arrays. We found that the gene expression changes caused by the gp120s of Subtypes A and B are different. Specifically, Subtype A is a more potent downregulator of perostasin, matrix metalloproteinase-2 (MMP-2), and ErbB/Her3 than Subtype B, while Subtype B is more effective in downregulating monocyte chemotactic protein-2 (MCP-2/CCL8), MCP-3 (CCL7), and thymus- and activation-regulated chemokine (TARC/CCL17) proteins. This is the first report of gp120 proteins affecting host cells in an HIV subtype-specific manner, opening up the possibility that vascular complications may occur differently in HIV patients throughout the world.
心血管并发症在人类免疫缺陷病毒（HIV）阳性个体中较为常见，由于抗逆转录病毒疗法的成功应用，这些个体现在能够存活更长时间。其中，肺动脉高压（PAH）是一种致命疾病，其特征是由于血管收缩和血管壁重塑导致肺循环血压升高，进而使心脏负担过重。HIV阳性人群中PAH的患病率显著高于普通人群。虽然HIV-1 M组B亚型是西方国家最常见的亚型，但东非和前苏联国家的大多数HIV-1感染是由A亚型引起的。然而，关于HIV阳性人群血管并发症机制的研究，尤其是在亚型差异背景下的研究并不严谨。许多关于HIV的研究都集中在B亚型上，而关于A亚型分子机制的信息则不存在。这种知识的缺乏导致在预防/治疗HIV并发症的治疗策略开发中出现健康差异。本研究通过进行蛋白质阵列实验，研究了A亚型和B亚型的HIV-1病毒融合蛋白gp120对培养的人肺动脉内皮细胞的影响。我们发现，A亚型和B亚型的gp120引起的基因表达变化是不同的。具体而言，与B亚型相比，A亚型对骨膜素、基质金属蛋白酶-2（MMP-2）和ErbB/Her3的下调作用更强，而B亚型在下调单核细胞趋化蛋白-2（MCP-2/CCL8）、MCP-3（CCL7）和胸腺激活调节趋化因子（TARC/CCL17）蛋白方面更有效。这是首次报道gp120蛋白以HIV亚型特异性方式影响宿主细胞，这为世界各地HIV患者可能以不同方式发生血管并发症开辟了可能性。
