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全球HIV-1分子流行病学,特别提及在印度北部流行的HIV-1亚型的基因分析:基因变异的功能和致病意义。

Global HIV-1 molecular epidemiology with special reference to genetic analysis of HIV-1 subtypes circulating in North India: functional and pathogenic implications of genetic variation.

作者信息

Neogi Ujjwal, Sood Vikas, Banerjee Snigdha, Ghosh Nilanjana, Verma Sachin, Samrat Subodh, Sharma Yogeshwar, Saxena Abhishek, Husain Sajid, Ramachandran V G, Das S, Sreedhar K Vijesh, Goel Nidhi, Wanchu Ajay, Banerjea Akhil C

机构信息

Laboratory of Virology II, National Institute of Immunology, New Delhi 110 067, India.

出版信息

Indian J Exp Biol. 2009 Jun;47(6):424-31.

Abstract

HIV-1 displays extensive genetic diversity globally which poses challenge in designing a suitable antigen/immunogen to provoke desired protective immune response in host. HIV-1 mediated pathogenesis is complex and involves host genes, virus genes and other factors. A number of genetic subtypes have been identified based on sequence variations, largely in envelope region. Different genetic subtypes display variation in amino acid sequences with increasing incidence of subtype B, C, D and mosaic recombinants in India. They can potentially alter the functions of several proteins like Rev, Tat ,Vpr, Vif etc and thereby, influence HIV-1 mediated pathogenesis. Recent study has shown that LTR promoter region exhibits novel mosaic structures with segments from B/C Myanmar and India. This indicates rapid evolving nature of HIV-1 and causing epidemics due to existence of multiple subtypes in Indian region. These multiple subtypes show significant differences in various functions (gene activation, cell cycle arrest, RNA binding activities) compared to prototype subtype B genes. These differences may help in better understanding of unique features of HIV-1 epidemic in India.

摘要

HIV-1在全球呈现出广泛的基因多样性,这给设计合适的抗原/免疫原以激发宿主所需的保护性免疫反应带来了挑战。HIV-1介导的发病机制很复杂,涉及宿主基因、病毒基因和其他因素。基于序列变异,主要是包膜区域的序列变异,已鉴定出多种基因亚型。不同的基因亚型在氨基酸序列上存在差异,在印度,B、C、D亚型和嵌合重组体的发病率不断上升。它们可能会改变Rev、Tat、Vpr、Vif等多种蛋白质的功能,从而影响HIV-1介导的发病机制。最近的研究表明,LTR启动子区域呈现出具有来自缅甸和印度的B/C片段的新型嵌合结构。这表明HIV-1具有快速进化的特性,并由于印度地区存在多种亚型而导致疫情爆发。与原型B亚型基因相比,这些多种亚型在各种功能(基因激活、细胞周期停滞、RNA结合活性)上存在显著差异。这些差异可能有助于更好地理解印度HIV-1疫情的独特特征。

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