Bukh J, Apgar C L
Hepatitis Viruses Section, National Institute of Allergy and infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0740, USA.
Virology. 1997 Mar 17;229(2):429-36. doi: 10.1006/viro.1997.8461.
In previous studies, human hepatitis viruses have been experimentally transmitted to New World monkeys of the genus Saguinus (tamarins). Recently, two Flaviviridae-like agents (GBV-A and GBV-B) were identified in tamarins that developed hepatitis following inoculation with serum of the 11th tamarin passage of a potentially new human hepatitis agent. However, it was not shown that these viruses originated from the initial inoculum. We here report the discovery of indigenous species-specific viruses related to GBV-A in several species of New World monkeys and suggest that GBV-A virus was fortuitously acquired during passage in tamarins. Sera or plasma from 98 wild-caught New World monkeys representing 10 different species was tested by RT-PCR with conserved degenerate primers to the 5' noncoding region of the genome. Viral sequences were identified in 33 animals and sequence analysis was performed on the amplicons. In addition, the genomic region corresponding to the putative NS3 RNA helicase of GBV-A was amplified from most positive animals and sequenced. We detected GBV-A-like viruses in 13 (35%) of 37 S. mystax, 7 (78%) of 9 S. nigricollis, 3 (25%) of 12 S. labiatus, 2 (50%) of 4 S. oedipus, 2 (100%) of 2 Callithrix jacchus, and 6 (50%) of 12 Aotus trivirgatus monkeys. Each positive animal was infected with a unique strain of the GBV-A-like viruses. Analysis of the 5' NC and NS3 helicase sequences revealed that these viruses could be classified into 5 major genetic groups with genetic distances equivalent to or greater than those found among major genetic groups of hepatitis C virus. Species-specific GBV-A-like viruses were found in S. mystax, S. nigricollis, S. oedipus, C. jacchus, and A. trivirgatus species. The viruses specific for S. nigricollis were closely related to GBV-A, suggesting that GBV-A was acquired by passage through this species during the initial transmission studies. The natural history of the GBV-A-like viruses was studied in serial serum samples from 9 S. mystax and 2 A. trivirgatus monkeys. Each animal was chronically infected and the viral strain did not vary during 9-27 months of follow-up. Finally, we demonstrated that four S. mystax were positive upon arrival to the United States from the country of origin. No apparent disease was associated with chronic infection of the GBV-A-like viruses. In conclusion, many New World monkeys are persistently infected with indigenous species-specific viruses that may represent a new genus within the virus family Flaviviridae.
在先前的研究中，人类肝炎病毒已通过实验性传播给狨属（绢毛猴）的新大陆猴。最近，在接种了一种潜在新型人类肝炎病原体第11代绢毛猴传代血清后发生肝炎的绢毛猴中，鉴定出两种黄病毒科样病原体（GBV - A和GBV - B）。然而，并未表明这些病毒源自最初的接种物。我们在此报告在几种新大陆猴中发现了与GBV - A相关的本土物种特异性病毒，并表明GBV - A病毒是在绢毛猴传代过程中偶然获得的。用针对基因组5'非编码区的保守简并引物通过逆转录聚合酶链反应（RT - PCR）检测了来自代表10个不同物种的98只野生捕获新大陆猴的血清或血浆。在33只动物中鉴定出病毒序列，并对扩增子进行了序列分析。此外，从大多数阳性动物中扩增出与GBV - A假定的NS3 RNA解旋酶相对应的基因组区域并进行测序。我们在37只白领伶猴中的13只（35%）、9只黑冠伶猴中的7只（78%）、12只白唇伶猴中的3只（25%）、4只普通狨中的2只（50%）、2只黑掌狨中的2只（100%）以及12只三带夜猴中的6只（50%）中检测到了GBV - A样病毒。每只阳性动物都感染了一种独特的GBV - A样病毒株。对5'非编码区（NC）和NS3解旋酶序列的分析表明，这些病毒可分为5个主要遗传组，其遗传距离等于或大于丙型肝炎病毒主要遗传组之间的遗传距离。在白领伶猴、黑冠伶猴、普通狨、黑掌狨和三带夜猴物种中发现了物种特异性的GBV - A样病毒。黑冠伶猴特有的病毒与GBV - A密切相关，这表明在最初的传播研究中，GBV - A是通过该物种传代获得的。在来自9只白领伶猴和2只三带夜猴的系列血清样本中研究了GBV - A样病毒的自然史。每只动物都被慢性感染，并且在9至27个月的随访期间病毒株没有变化。最后，我们证明4只白领伶猴从原产国抵达美国时呈阳性。GBV - A样病毒的慢性感染未伴有明显疾病。总之，许多新大陆猴持续感染本土物种特异性病毒，这些病毒可能代表黄病毒科病毒家族中的一个新属。
