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对从不同临床特征感染个体中分离出的1型人类T细胞白血病病毒的HBZ和gp21蛋白的分子研究。

Molecular study of HBZ and gp21 human T cell leukemia virus type 1 proteins isolated from different clinical profile infected individuals.

作者信息

Mota-Miranda Aline Cristina A, Barreto Fernanda K, Baptista Everton, Farre-Vale Lourdes, Monteiro-Cunha Joana P, Galvão-Castro Bernardo, Alcantara Luiz Carlos J

机构信息

1 Centro de Pesquisa Gonçalo Moniz , Fundação Oswaldo Cruz, Salvador, Bahia, Brazil .

出版信息

AIDS Res Hum Retroviruses. 2013 Oct;29(10):1370-2. doi: 10.1089/AID.2013.0015. Epub 2013 Aug 21.

DOI:10.1089/AID.2013.0015
PMID:23800288
Abstract

Human T cell leukemia virus type 1 (HTLV-1) is associated with a neurological syndrome named tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) and the disease progression involves viral factors. The gp21 glycoprotein is involved in envelope trafficking and membrane targeting while the bZIP protein is indispensable for cell growth and proliferation. This study aimed to assess the molecular diversity of gp21 and HBZ proteins in TSP/HAM and healthy carriers. DNA samples from HTLV-1-infected individuals were submitted to PCR and sequencing, and the molecular analyses were performed using bioinformatics tools. From eight gp21-analyzed sequences one amino acid change (Y477H) was associated with the switch of a helix to coil structure at secondary structure prediction. From 10 HBZ analyzed sequences, two amino acid changes were identified (S9P and T95I) at the activation domain. One mutation (R112C) located at the nuclear localization signal was present in 66.7% and 25% of healthy carriers (HC) and TSP/HAM groups, respectively. This is the first report of mutations in the HBZ region. These polymorphisms might be important for viral fitness.

摘要

人类嗜T淋巴细胞病毒1型(HTLV-1)与一种名为热带痉挛性截瘫/HTLV相关脊髓病(TSP/HAM)的神经综合征有关,且疾病进展涉及病毒因素。gp21糖蛋白参与包膜运输和膜靶向,而碱性亮氨酸拉链(bZIP)蛋白对细胞生长和增殖不可或缺。本研究旨在评估TSP/HAM患者和健康携带者中gp21和HBZ蛋白的分子多样性。将HTLV-1感染个体的DNA样本进行PCR和测序,并使用生物信息学工具进行分子分析。在分析的8条gp21序列中,一个氨基酸变化(Y477H)在二级结构预测中与螺旋结构向卷曲结构的转变相关。在分析的10条HBZ序列中,在激活域鉴定出两个氨基酸变化(S9P和T95I)。位于核定位信号的一个突变(R112C)分别在66.7%的健康携带者(HC)组和25%的TSP/HAM组中出现。这是HBZ区域突变的首次报道。这些多态性可能对病毒适应性很重要。

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