An Observational Study of Genetic Diversity of HIV-1 vpu in Rapid Progressors in India.

IF 0.8 4区 医学 Q4 IMMUNOLOGY
Poonam Gupta, Arvind Rai, Charoo Hans, Mohammad Husain
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引用次数: 0

Abstract

Background: The genetic diversity in HIV-1 genes affects viral pathogenesis in HIV-1 positive patients. Accessory genes of HIV-1, including vpu, are reported to play a critical role in HIV pathogenesis and disease progression. Vpu has a crucial role in CD4 degradation and virus release. The sequence heterogeneity in the vpu gene may affect disease progression in patients, therefore, the current study was undertaken to identify the role of vpu in patients defined as rapid progressors.

Objective: The objective of the study was to identify the viral determinants present on vpu that may be important in disease progression in rapid progressors.

Methods: Blood samples were collected from 13 rapid progressors. DNA was isolated from PBMCs and vpu was amplified using nested PCR. Both strands of the gene were sequenced using an automated DNA Sequencer. The characterization and analysis of vpu was done using various bioinformatics tools.

Results: The analysis revealed that all sequences had intact ORF and sequence heterogeneity was present across all sequences and distributed all over the gene. The synonymous substitutions, however, were higher than nonsynonymous substitutions. The phylogenetic tree analysis showed an evolutionary relationship with previously published Indian subtype C sequences. Comparatively, the cytoplasmic tail(77 - 86) showed the highest degree of variability in these sequences as determined by Entropy- one tool.

Conclusion: The study showed that due to the robust nature of the protein, the biological activity of the protein was intact and sequence heterogeneity may promote disease progression in the study population.

印度HIV-1 vpu快速进展者遗传多样性的观察研究
背景:HIV-1基因的遗传多样性影响HIV-1阳性患者的病毒发病机制。据报道,HIV-1的辅助基因,包括vpu,在HIV的发病机制和疾病进展中起关键作用。Vpu在CD4降解和病毒释放中起关键作用。vpu基因的序列异质性可能影响患者的疾病进展,因此,本研究旨在确定vpu在快速进展患者中的作用。目的:该研究的目的是确定vpu上存在的病毒决定因素,这可能是快速进展患者疾病进展的重要因素。方法:采集13例快速进展患者的血样。从PBMCs中分离DNA,用巢式PCR扩增vpu。基因的两条链都是用自动DNA测序仪测序的。利用各种生物信息学工具对vpu进行了表征和分析。结果:分析结果显示,所有序列均具有完整的ORF,且序列异质性存在于所有序列之间,并分布于整个基因。然而,同义替换高于非同义替换。系统发育树分析显示了与先前发表的印度C亚型序列的进化关系。相比之下,细胞质尾部(77 - 86)在这些序列中显示出最高程度的变异,由熵一工具确定。结论:研究表明,由于该蛋白的健壮性,该蛋白的生物活性是完整的,序列异质性可能促进研究人群的疾病进展。
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来源期刊
Current HIV Research
Current HIV Research 医学-病毒学
CiteScore
1.90
自引率
10.00%
发文量
81
审稿时长
6-12 weeks
期刊介绍: Current HIV Research covers all the latest and outstanding developments of HIV research by publishing original research, review articles and guest edited thematic issues. The novel pioneering work in the basic and clinical fields on all areas of HIV research covers: virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Periodically, the journal invites guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.
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