Hait Sabrina H, Soares Esmeralda A, Sprinz Eduardo, Arthos James, Machado Elizabeth S, Soares Marcelo A
*Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; †Programa de Oncovirologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; ‡Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil; §Laboratory of Immune Regulation, National Institutes of Health, Bethesda, MD; and ‖Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
J Acquir Immune Defic Syndr. 2015 Dec 15;70(5):463-71. doi: 10.1097/QAI.0000000000000802.
HIV-1 gp120 binds to integrin α4β7, a homing receptor of lymphocytes to gut-associated lymphoid tissues. This interaction is mediated by the LDI/V tripeptide encoded in the V2-loop. This tripeptide mimics similar motifs in mucosal addressin cellular adhesion molecule (MAdCAM) and vascular CAM (VCAM), the natural ligands of α4β7. In this study, we explored the association of V2-loop LDI/V mimotopes with transmission routes and patterns of disease progression in HIV-infected adult and pediatric patients. HIV-1 env sequences available in the Los Alamos HIV Sequence database were included in the analyses.
HIV-1 V2-loop sequences generated from infected adults and infants from South and Southeast Brazil, and also retrieved from the Los Alamos database, were assessed for α4β7 binding tripeptide composition. Chi-Square/Fisher Exact test and Mann Whitney U test were used for tripeptide comparisons. Shannon entropy was assessed for conservancy of the α4β7 tripeptide mimotope.
We observed no association between the tripeptide composition or conservation and virus transmission route or disease progression. However, LDI was linked to successful epidemic dissemination of HIV-1 subtype C in South America, and further to other expanding non-B subtypes in Europe and Asia. In Africa, subtypes showing increased LDV prevalence evidenced an ongoing process of selection toward LDI expansion, an observation also extended to subtype B in the Americas and Western Europe.
The V2-loop LDI mimotope was conserved in HIV-1C from South America and other expanding subtypes across the globe, which suggests that LDI may promote successful dissemination of HIV at local geographic levels by means of increased transmission fitness.
HIV-1 gp120与整合素α4β7结合，α4β7是淋巴细胞归巢至肠道相关淋巴组织的受体。这种相互作用由V2环中编码的LDI/V三肽介导。该三肽模拟黏膜地址素细胞黏附分子（MAdCAM）和血管细胞黏附分子（VCAM）中的相似基序，而MAdCAM和VCAM是α4β7的天然配体。在本研究中，我们探讨了V2环LDI/V模拟表位与HIV感染的成人及儿童患者的传播途径和疾病进展模式之间的关联。分析纳入了洛斯阿拉莫斯HIV序列数据库中可用的HIV-1 env序列。
对来自巴西南部和东南部感染成人及婴儿的HIV-1 V2环序列，以及从洛斯阿拉莫斯数据库中检索到的序列，评估其α4β7结合三肽组成。采用卡方检验/费舍尔精确检验和曼-惠特尼U检验进行三肽比较。评估香农熵以确定α4β7三肽模拟表位的保守性。
我们观察到三肽组成或保守性与病毒传播途径或疾病进展之间无关联。然而，LDI与HIV-1 C亚型在南美洲的成功流行传播相关，还与欧洲和亚洲其他正在扩展的非B亚型相关。在非洲，显示LDV流行率增加的亚型表明正在朝着LDI扩展的方向进行选择，这一观察结果也扩展到美洲和西欧的B亚型。
V2环LDI模拟表位在来自南美洲的HIV-1 C型及全球其他正在扩展的亚型中是保守的，这表明LDI可能通过提高传播适应性在局部地理区域促进HIV的成功传播。
