Origin and evolution of GBV-C/hepatitis G virus and relationships with ancient human migrations

The GB virus C/hepatitis G virus (GBV-C/HGV) is a newly identified human RNA virus, belonging to the Flaviviridae family. Persistent infection by GBV-C/HGV is common in humans, and genetically divergent isolates have been identified in different parts of the world. Due to the absence of a real pathogenic role of GBV-C/HGV in liver disease and its extremely low mutation rate, this virus is a potential marker to trace prehistoric links between human populations. In this study, origin and evolution of GBV-C/HGV were examined using a set of fully sequenced strains of worldwide origin. A first phylogenetic analysis, addressed to the short (255 nucleotides) NS5A overlapping coding region by the neighbor-joining method, suggested an ancient African origin of GBV-C/HGV. This notion was confirmed when the same analysis was applied to the genomic regions showing the lowest rate of synonymous substitutions, covering one-fourth (2184 nucleotides) of the total coding potential of the virus genome. By using a multivariate statistical method and extending the analysis to the complete coding region, fine details of the evolutionary history of GBV-C/HGV were further elucidated. By this approach, isolates from Southeast Asia appeared to be the most closely related to those of African origin, consistent with a major route of ancient human migrations from Africa to southeastern parts of the Asian continent. Received: 26 October 2000 / Accepted: 28 February 2001     

庚型肝炎病毒NS3蛋白在昆虫细胞中的表达

庚型肝炎病毒(HGV)/GB病毒C(GBV-C)疑似引起人类庚型肝炎[1～3].HGV和GBV-C为同一病毒的两个不同分离株,本文将其称为GBV-C/HGV.GBV-C/HGV属黄病毒科,为单股正链RNA病毒,全长约9.4kb.基因组中仅含有一个单一开放阅读框,编码E1、E2结构蛋白和NS2、NS3、NS4及NS5非结构蛋白.GBV-C/HGV的NS3蛋白具备丝氨酸蛋白酶活性和解旋酶活性[3],在NS3蛋白中还存在线性抗原表位[4],因此,NS3蛋白是GBV-C/HGV的重要功能蛋白.     

GBV-C/HIV共感染对AIDS疾病进程和HIV病毒复制的影响

近年来,一些研究发现,GBV-C/HIV共感染可延缓HIV感染疾病的进程,然而也有一些研究得出不同的结论.本研究收集我国安徽省阜阳市HIV血清学阳性的既往献血员血浆标本,对其进行GBV-C感染的检测,研究GBV-C/HIV共感染与HIV病毒载量和CD4 T淋巴细胞绝对计数的关系.用RT-PCR和酶联免疫法检测,在203人中检出GBV-C感染52例,显示该人群GBV-C的感染率为25.6%,男性感染者(35例,67.3%)高于女性感染者(17例,32.7%).分析发现,GBV-C感染与未感染两组患者的CD4 T淋巴细胞绝对计数和HIV病毒载量数据均无统计学差异.本研究中的HIV-1感染者均未接受ART治疗,因而排除了治疗对疾病进展的影响.研究结果显示,在HIV-1感染晚期的献血人群,GBV-C/HIV共感染对CD4细胞和病毒复制水平无显著影响.由于本研究对象中无HIV-1早期感染者,因而不能判断GBV-C在HIV-1感染的早期对疾病进展有无影响.     

GBV-C与艾滋病毒的相互作用及其机制

GBV-C（GB Virus C)是20世纪90年代中期发现的一种单股正链RNA病毒,属黄病毒科Pegivirus属,全基因组长约9.4 kb,编码约2 900个氨基酸序列.早期认为,该病毒与肝炎有关,但随后的研究发现,该病毒对人类无致病作用.最近的研究表明,GBV-C与艾滋病毒（人类免疫缺陷病毒,human immunodeficiency virus,HIV）共感染情况下可抑制HIV的增殖、提高机体免疫、延缓HIV 患者疾病进程.进一步研究GBV-C与HIV的相互作用及其机制可能会为艾滋病（acquired immune deficiency syndrome,AIDS）治疗提供新思路. 本文就GBV-C与HIV-1相互作用的两种主要类型--间接和直接的作用以及其机制进行了综述.     

Slow Evolutionary Rate of GB Virus C/Hepatitis G Virus

With the aim of elucidating evolutionary features of GB virus C/hepatitis G virus (GBV-C/HGV), molecular evolutionary analyses were conducted using the entire coding region of this virus. In particular, the rate of nucleotide substitution for this virus was estimated to be less than 9.0 × 10⁻⁶ per site per year, which was much slower than those for other RNA viruses. The phylogenetic tree reconstructed for GBV-C/HGV, by using GB virus A (GBV-A) as outgroup, indicated that there were three major clusters (the HG, GB, and Asian types) in GBV-C/HGV, and the divergence between the ancestor of GB- and Asian-type strains and that of HG-type strains first took place more than 7000–10,000 years ago. The slow evolutionary rate for GBV-C/HGV suggested that this virus cannot escape from the immune response of the host by means of producing escape mutants, implying that it may have evolved other systems for persistent infection. Received: 2 June 1998 / Accepted: 8 August 1998