发现自然发生传染性的慢性乙肝病毒感染食蟹猴从毛里求斯

StephenW

Hepatology. 2013 Mar 27. doi: 10.1002/hep.26428. [Epub ahead of print]
Discovery of naturally occurring transmissible chronic hepatitis B virus infection among Macaca fascicularis from Mauritius Island.
Dupinay T, Gheit T, Roques P, Cova L, Chevallier-Queyron P, Tasahsu SI, Grand RL, Simon F, Cordier G, Wakrim L, Benjelloun S, Trépo C, Chemin I.
Source

Université de Lyon, F6900 Lyon, France; INSERM U1052, Centre de Recherche en Cancérologie de Lyon, F-69003 Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69003 Lyon, France; Ecole pratique des hautes études (EPHE), Paris, France.
Abstract

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, non-human 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 macaques cynomolgus (M.fascicularis) from Mauritius Island only and, remarkably, HBV DNA was positive in 25.8% (31/120) and 42% (21/of 50) of serum and liver samples, respectively. Strong liver expression of HBsAg and HBcAg was detected in about 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 the infectivity of this isolate, 3 M.sylvanus were inoculated with a pool of M.fascicularis serum and developed an acute HBV infection with 100% sequence homology compared to HBV inoculum. In conclusion, 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 man, since the initial breading colony originated from very few ancestors three hundred years ago when it was implemented by Portuguese who imported a handful of macaques from Java to Mauritius Island. This report on natural, persisting HBV infection amongst Cynomolgus macaques provides the first evidence for the existence of a novel, small simian model of chronic HBV infection, immunologically close to human, should be most valuable for the study of immunotherapeutic approaches against chronic hepatitis B. (HEPATOLOGY 2013.).

Copyright © 2013 American Association for the Study of Liver Diseases.

StephenW

尽管B型肝炎病毒（HBV）感染在濒临灭绝的猿类的患病率较高，无乙肝病毒感染已报道在旧世界的小猴子。寻找一个小的，非人类灵长类动物模型中，我们调查了260猕猴（猴科）不同的地理起源，即摩洛哥，毛里求斯岛和亚洲血清中HBV感染的患病率。显着，仅毛里求斯岛食蟹猕猴（ M.fascicularis ）的从检测乙肝标志物阳性， HBV-DNA是阳性血清和肝脏样本的25.8％ （31/ 120）和42 ％ （ 21/of 50 ） ，分别。强肝检测HBsAg和HBcAg表达约20-30 ％的肝细胞。此外，慢性感染与坚持HBV DNA被记录在所有6感染的猕猴，在8个月的随访期间。 HBV全基因组测序数据显示，这是基因型的D亚型ayw3账面替代67位前S1 。要确认此分离物的感染性接种一池M.fascicularis血清和3 M.sylvanus ，开发了一种与100％的序列同源性的急性HBV感染HBV接种相比。总之，我们证明了存在的慢性HBV感染在M.fascicularis从毛里求斯岛。此人密切相关的乙肝病毒可能已经从人传播，从最初的面包屑殖民地源于极少数的祖先三百年前，当它是由葡萄牙实施了一把进口的猕猴从Java到毛里求斯岛。自然，坚持HBV感染之间的食蟹猕猴本报告提供的首个证据存在的一本小说，小猿慢性HBV感染模型，免疫接近人类，应该是最有价值的，对慢性乙型肝炎的免疫治疗方法的研究（肝病2013 ） 。