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首页> 外文期刊>Journal of Medical Virology >Genetic attributes of blood-derived subtype-C HIV-1 tat and env in India and neurocognitive function
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Genetic attributes of blood-derived subtype-C HIV-1 tat and env in India and neurocognitive function

机译：印度血液来源的C型亚型HIV-1 tat和env的遗传属性和神经认知功能

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摘要

Genetic elements in HIV-1 subtype B tat and env are associated with neurotoxicity yet less is known about other subtypes. HIV-1 subtype C tat and env sequences were analyzed to determine viral genetic elements associated with neurocognitive impairment in a large Indian cohort. Population-based sequences of HIV-1 tat (exon 1) and env (C2-V3 coding region) were generated from blood plasma of HIV-infected patients in Pune, India. Participants were classified as cognitively normal or impaired based on neuropsychological assessment. Tests for signature residues, positive and negative selection, entropy, and ambiguous bases were performed using tools available through Los Alamos National Laboratory (http://www.hiv.lanl.gov) and Datamonkey (http://www.datamonkey.org). HIV-1 subtype C tat and env sequences were analyzed for 155 and 160 participants, of which 34-36% were impaired. Two signature residues were unique to impaired participants in exon 1 of tat at codons 29 (arginine) and 68 (proline). Positive selection was noted at codon 29 among normal participants and at codon 68 in both groups. The signature at codon 29 was also a signature for low CD4+ (200cells/mm3) counts but remained associated with impairment after exclusion of those with low CD4+ counts. No unique genetic signatures were noted in env. In conclusion, two signature residues were identified in exon 1 of HIV-1 subtype C tat that were associated with neurocognitive impairment in India and not completely accounted for by HIV disease progression. These signatures support a linkage between diversifying selection in HIV-1 subtype C tat and neurocognitive impairment.
机译：HIV-1 B亚型tat和env中的遗传成分与神经毒性有关，但对其他亚型的了解较少。分析了HIV-1亚型C tat和env序列，以确定与印度大型队列中神经认知障碍相关的病毒遗传元件。 HIV-1 tat（外显子1）和env（C2-V3编码区）基于人群的序列是从印度浦那的HIV感染患者的血浆中产生的。根据神经心理学评估，参与者被分类为认知正常或障碍者。使用可通过洛斯阿拉莫斯国家实验室（http://www.hiv.lanl.gov）和Datamonkey（http://www.datamonkey.org）获得的工具对特征残基，正负选择，熵和模棱两可的碱基进行测试。 ）。分析了155位和160位参与者的HIV-1亚型C tat和env序列，其中34-36％的患者受损。对于tat外显子1受损的参与者，两个标记残基是唯一的，密码子为29（精氨酸）和68（脯氨酸）。正常参与者的密码子为29，两组的密码子为68。第29位密码子的特征也是CD4 +含量低（<200cells / mm3）的特征，但在排除CD4 +含量低的特征后仍与损伤相关。在环境中没有发现独特的遗传特征。总之，在印度的HIV-1亚型tat的第1外显子中鉴定出两个特征性残基，它们与印度的神经认知功能障碍有关，并未完全由HIV疾病的进展解释。这些签名支持在HIV-1亚型C tat中的多样化选择与神经认知障碍之间的联系。

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