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分析 HIV 感染者和健康供体尿液中 JC 病毒株的变异性。

Analysis of variability of urinary excreted JC virus strains in patients infected with HIV and healthy donors.

机构信息

Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia, Dr Subotica 1, Belgrade, 11000, Serbia.

Clinics of Infectious and Tropical Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbia, Bulevar oslobodjenja 16, Belgrade, 11000, Serbia.

出版信息

J Neurovirol. 2018 Jun;24(3):305-313. doi: 10.1007/s13365-017-0608-y. Epub 2017 Dec 14.

Abstract

In immunocompromised individuals, especially in patients with T cell immunodeficiency, reactivation of JCPyV can cause serious life-threatening diseases. Nowadays, HIV infection is one of the most important factor for reactivation of JCPyV and the development of of the progressive multifocal leukoencephalopathy (PML). Mutations in the outer loops of the VP1 region can lead to the selection of the viral variants with changed tropism and increased pathological potential. The aims of this study were to determine sequence variation and amino acid changes within VP1 loops and the structure of non-coding control region (NCCR) of urinary excreted JCPyV isolates among HIV-infected patients and healthy donors. Single urine samples from 114 HIV-infected patients and 120 healthy donors were collected. PCR was performed for amplification of VP1 and NCCR. Amplified fragments were directly sequenced and analyzed by using bioinformatics tools. Nucleotide substitutions were detected within DE and EF loops and in the β-sheets of both studied groups. In HIV-infected patients group, 70% of mutations were detected within receptor domains. Among healthy donors, one mutation was identified within β-sheets while the remaining were located within receptor domains. The most prevalent mutation was L157V in both groups. Analysis of NCCR revealed that all isolates had archetype structure with some minor changes. Since single point mutations at specific place within outer loop of VP1 region can cause formation of variants with changed receptor specificity, identification of these mutations in HIV-infected patients can help to single out those with higher risk for development of polyomavirus-associated diseases.

摘要

在免疫功能低下的个体中,特别是 T 细胞免疫缺陷患者中,JCPyV 的再激活可导致严重的危及生命的疾病。如今,HIV 感染是 JCPyV 再激活和进行性多灶性白质脑病(PML)发展的最重要因素之一。VP1 区域外环突变可导致选择具有改变的嗜性和增加的病理潜能的病毒变异体。本研究的目的是确定 HIV 感染患者和健康供体尿液中排泄的 JCPyV 分离株 VP1 环内和非编码控制区(NCCR)的序列变异和氨基酸变化以及结构。从 114 名 HIV 感染患者和 120 名健康供体中采集单个尿液样本。进行 PCR 以扩增 VP1 和 NCCR。直接对扩增片段进行测序,并通过生物信息学工具进行分析。在 DE 和 EF 环内以及两个研究组的 β-片层中均检测到核苷酸取代。在 HIV 感染患者组中,70%的突变发生在受体结构域内。在健康供体中,一个突变发生在β-片层内,其余突变发生在受体结构域内。两个组中最常见的突变是 L157V。NCCR 的分析表明,所有分离株均具有原型结构,伴有一些微小变化。由于 VP1 区域外环中特定位置的单点突变可导致受体特异性改变的变异体形成,因此在 HIV 感染患者中鉴定这些突变可以帮助确定那些发生多瘤病毒相关疾病风险较高的患者。

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