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俄罗斯1型艾滋病毒变体的分子流行病学及MT-2细胞嗜性

Molecular epidemiology and MT-2 cell tropism of Russian HIV type 1 variant.

作者信息

Leitner T, Korovina G, Marquina S, Smolskaya T, Albert J

机构信息

Department of Clinical Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden.

出版信息

AIDS Res Hum Retroviruses. 1996 Nov 20;12(17):1595-603. doi: 10.1089/aid.1996.12.1595.

Abstract

Twenty-two HIV-1-infected Russian individuals were studied to gain better insight on the genetic and biological characteristics of HIV-1 variants present in Russia. The V3 domain of the HIV-1 envelope was directly sequenced from cultured peripheral blood mononuclear cells (PBMCs). Phylogenetic analyses were used to determine the HIV-1 genetic subtype and to study transmission patterns. Virus isolates were obtained from PBMCs and the biological phenotype was determined by coculture with MT-2, CEM, and Jurkat-tat cells. Twelve homo- and bisexual men carried subtype B variants, whereas 6 heterosexually infected individuals carried subtype F virus. A heterosexual man infected in the Ivory Coast and a nosocomially infected young female carried subtype A and G virus, respectively. Interestingly, phylogenetic analyses suggested that subtype B may have entered Russia on at least four occasions and, even more surprisingly, that the relatively rare subtype F has entered Russia on at least three occasions. Two suspected transmission clusters of subtype F were supported by the phylogenetic analyses, whereas one suspected subtype B transmission cluster was not. Positively charged amino acids in positions 311 and 325 of V3 loop have been shown to be important determinants for the MT-2-positive biological phenotype of virus isolates. Interestingly, we found that the direct PBMC sequences from individuals with MT-2-positive isolates displayed specific neutral, instead of positively charged, amino acids, in these positions. This indicates that it may be more difficult to predict the biological phenotype of HIV-1 using sequences from uncultured PBMCs than from virus isolates.

摘要

对22名感染HIV-1的俄罗斯人进行了研究,以更深入地了解俄罗斯境内HIV-1变体的遗传和生物学特征。从培养的外周血单核细胞(PBMC)中直接对HIV-1包膜的V3结构域进行测序。系统发育分析用于确定HIV-1基因亚型并研究传播模式。从PBMC中获得病毒分离株,并通过与MT-2、CEM和Jurkat-tat细胞共培养来确定生物学表型。12名男同性恋者和双性恋者携带B亚型变体,而6名异性感染个体携带F亚型病毒。一名在象牙海岸感染的异性恋男子和一名医院感染的年轻女性分别携带A亚型和G亚型病毒。有趣的是,系统发育分析表明,B亚型可能至少四次传入俄罗斯,更令人惊讶的是,相对罕见的F亚型至少三次传入俄罗斯。系统发育分析支持了两个疑似F亚型传播簇,而一个疑似B亚型传播簇则未得到支持。V3环第311和325位带正电荷的氨基酸已被证明是病毒分离株MT-2阳性生物学表型的重要决定因素。有趣的是,我们发现,来自MT-2阳性分离株个体的直接PBMC序列在这些位置显示出特定的中性而非带正电荷的氨基酸。这表明,使用未培养PBMC的序列预测HIV-1的生物学表型可能比使用病毒分离株的序列更困难。

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