Chang Qing, McLinden James H, Stapleton Jack T, Sathar M Aslam, Xiang Jinhua
Iowa City VA Medical Center and the University of Iowa, Iowa City, IA 52246, USA.
Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, South Africa.
J Gen Virol. 2007 Dec;88(Pt 12):3341-3346. doi: 10.1099/vir.0.83198-0.
GB virus type C (GBV-C) is a common human flavivirus that has been associated with prolonged survival in HIV-positive individuals in several, though not all, epidemiological studies. There are five distinct GBV-C genotypes that are geographically localized, and it has been speculated that GBV-C genotypic differences may explain variable outcomes observed in different clinical studies. Expression of an 85 aa fragment of the GBV-C NS5A phosphoprotein (genotype 2) in a CD4+ T cell line (Jurkat) resulted in inhibition of HIV replication, mediated in part by decreased surface expression of the HIV coreceptor CXCR4 and upregulation of SDF-1. We expressed the NS5A protein from genotypes 1, 2, 3 and 5 in Jurkat cells, and demonstrated that all genotypes inhibited HIV replication. Further deletion mapping demonstrated that expression of a 30 aa fragment resulted in decreased CXCR4 surface expression, upregulation of SDF-1 and inhibition of HIV replication.
丙型肝炎病毒（GBV-C）是一种常见的人类黄病毒，在一些（尽管不是所有）流行病学研究中，它与HIV阳性个体的生存期延长有关。GBV-C有五种不同的基因型，在地理上有局限性，据推测，GBV-C基因型差异可能解释了不同临床研究中观察到的不同结果。在CD4+T细胞系（Jurkat）中表达GBV-C NS5A磷蛋白（基因型2）的一个85个氨基酸的片段，导致HIV复制受到抑制，部分是由HIV共受体CXCR4的表面表达减少和SDF-1的上调介导的。我们在Jurkat细胞中表达了基因型1、2、3和5的NS5A蛋白，并证明所有基因型都能抑制HIV复制。进一步的缺失图谱分析表明，一个30个氨基酸片段的表达导致CXCR4表面表达减少、SDF-1上调和HIV复制受到抑制。
