Discovery of Naturally Occurring Transmissible Chronic Hepatitis B Virus Infection Among Macaca fascicularis From Mauritius Island
Discovery of Naturally Occurring Transmissible Chronic Hepatitis B Virus Infection Among Macaca fascicularis From Mauritius Island
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DOI：
10.1002/hep.26428
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发表时间：
2013-11-01
期刊：
影响因子：
13.5
通讯作者：
Chemin, Isabelle
中科院分区：
文献类型：
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作者：
Dupinay, Tatiana;Gheit, Tarik;Chemin, Isabelle
尽管乙型肝炎病毒（HBV）感染在濒危类人猿中流行率很高，但在旧大陆的小猴子中没有HBV感染的报道。为了寻找一种小型的非人灵长类动物模型，我们调查了不同地理来源（即摩洛哥、毛里求斯岛和亚洲）的260只猕猴（猴尾科）血清中HBV感染的流行情况。仅在毛里求斯岛食蟹猴（Macaca fascicularis）中检测到HBV阳性标记物，值得注意的是，血清和肝脏样本中HBV DNA分别为25.8%（120 / 31）和42%（50 / 21）。在约20%-30%的肝细胞中检测到乙型肝炎表面抗原和乙型肝炎核心抗原的强烈表达。此外，在8个月的随访期间，所有6只受感染的猕猴都记录了持续HBV DNA的慢性感染。HBV全基因组测序数据显示其为基因型D亚型ayw3，在preS1的67位携带替换。为了证实该分离株的感染性，将3只猕猴接种一池束状分枝杆菌血清后，与HBV接种体相比，发生了序列同源性100%的急性HBV感染。我们证实了在毛里求斯岛的束状分枝杆菌中存在慢性HBV感染。这种与人类密切相关的HBV可能是从人类传播的，因为最初的繁殖群体起源于300年前的极少数祖先，当时葡萄牙人从爪哇向毛里求斯岛引进了少量猕猴。结论：这篇关于食蟹猕猴自然持续HBV感染的报道首次证明了一种新的小型猿类慢性HBV感染模型的存在，该模型在免疫学上与人类接近，应该对慢性乙型肝炎免疫治疗方法的研究最有价值（Hepatology 2013;58:1610-1620）。
Despite a high prevalence of hepatitis B virus (HBV) infection in endangered apes, no HBV infection has been reported in small, old-world monkeys. In search for a small, nonhuman primate model, we investigated the prevalence of HBV infection in 260 macaque (Cercopithecidae) sera of various geographical origins (i.e., Morocco, Mauritius Island, and Asia). HBV-positive markers were detected in cynomolgus macaques (Macaca fascicularis) from Mauritius Island only, and, remarkably, HBV DNA was positive in 25.8% (31 of 120) and 42% (21 of 50) of serum and liver samples, respectively. Strong liver expression of hepatitis B surface antigen and hepatitis B core antigen was detected in approximately 20%-30% of hepatocytes. Furthermore, chronic infection with persisting HBV DNA was documented in all 6 infected macaques during an 8-month follow-up period. Whole HBV genome-sequencing data revealed that it was genotype D subtype ayw3 carrying substitution in position 67 of preS1. To confirm infectivity of this isolate, 3 Macaca sylvanus were inoculated with a pool of M. fascicularis serum and developed an acute HBV infection with 100% sequence homology, compared with HBV inoculum. We demonstrated the presence of a chronic HBV infection in M. fascicularis from Mauritius Island. This closely human-related HBV might have been transmitted from humans, because the initial breeding colony originated from very few ancestors 300 years ago when it was implemented by Portuguese who imported a handful of macaques from Java to Mauritius Island. Conclusion: This report on natural, persisting HBV infection among cynomolgus macaques provides the first evidence for the existence of a novel, small simian model of chronic HBV infection, immunologically close to humans, that should be most valuable for the study of immunotherapeutic approaches against chronic hepatitis B. (Hepatology 2013;58:1610-1620)