Kaur Gurvinder, Sharma Gaurav, Kumar Neeraj, Kaul Mrinali H, Bansal Rhea A, Vajpayee Madhu, Wig Naveet, Sharma Surender K, Mehra Narinder K
Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
Indian J Med Res. 2013 Nov;138(5):663-81.
Studies on host genomics have revealed the existence of identifiable HIV-1 specific protective factors among infected individuals who remain naturally resistant viraemia controllers with little or no evidence of virus replication. These factors are broadly grouped into those that are immune associated (MHC, chemokines, cytokines, CTLs and others), linked to viral entry (chemokine co-receptors and ligands), act as post-entry restriction elements (TRIM5a, APOBEC3) and those associated with viral replication (cytokines and others). These features have been identified through multiple experimental approaches ranging from candidate gene approaches, genome wide association studies (GWAS), expression analysis in conjunction with functional assays in humans to primate based models. Several studies have highlighted the individual and population level gross differences both in the viral clade sequences as well as host determined genetic associations. This review collates current information on studies involving major histocompatibility complex (MHC) as well as non MHC genes in the context of HIV-1 infection and AIDS involving varied ethnic groups. Special focus of the review is on the genetic studies carried out on the Indian population. Further challenges with regard to therapeutic interventions based on current knowledge have been discussed along with discussion on documented cases of stem cell therapy and very early highly active antiretroviral therapy (HAART) interventions.
宿主基因组学研究表明,在那些自然抵抗病毒血症的感染者中,存在可识别的HIV-1特异性保护因子,这些感染者几乎没有或完全没有病毒复制的迹象。这些因子大致可分为免疫相关因子(MHC、趋化因子、细胞因子、细胞毒性T淋巴细胞等)、与病毒进入相关的因子(趋化因子共受体和配体)、作为病毒进入后限制元件的因子(TRIM5a、载脂蛋白B mRNA编辑酶催化多肽样蛋白3)以及与病毒复制相关的因子(细胞因子等)。这些特征是通过多种实验方法确定的,包括候选基因方法、全基因组关联研究(GWAS)、结合人类功能测定的表达分析以及基于灵长类动物的模型。多项研究强调了病毒分支序列以及宿主决定的基因关联在个体和群体水平上的显著差异。本综述整理了目前有关涉及不同种族群体的HIV-1感染和艾滋病背景下主要组织相容性复合体(MHC)以及非MHC基因研究的信息。该综述的特别关注点是对印度人群开展的基因研究。基于现有知识的治疗干预面临的进一步挑战也已得到讨论,同时还讨论了干细胞治疗和极早期高效抗逆转录病毒疗法(HAART)干预的记录案例。