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对从野生感染黑猩猩体内分离出的乙型肝炎病毒(HBV)毒株进行全基因组序列分析:对HBV起源的启示

Full-genome sequence analyses of hepatitis B virus (HBV) strains recovered from chimpanzees infected in the wild: implications for an origin of HBV.

作者信息

Takahashi K, Brotman B, Usuda S, Mishiro S, Prince A M

机构信息

Department of Medical Sciences, Toshiba General Hospital, 6-3-22 Higashi Oh-i, Tokyo, 140-8522, Japan.

出版信息

Virology. 2000 Feb 1;267(1):58-64. doi: 10.1006/viro.1999.0102.

DOI:10.1006/viro.1999.0102
PMID:10648183
Abstract

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the family Hepadnaviridae. Having been found in various animals (duck, heron, woodchuck, ground squirrel, and primates), hepadnaviruses must have undergone a long history of evolution and may comprise more members than currently recognized. Chimpanzees may also have their own hepadnavirus, even if it might be very close to HBV. We analyzed HBV-like sequences from three chimpanzees (Pan troglodytes) that were most likely infected during their life in Africa in the wild. Two chimpanzees (Ch256 and Ch258) possessed a viral genome of 3182 nt in length with a 33-nt deletion in the preS1 region, which could not be classified into any of the six genotypes (A-F) of human HBV but was very homologous to a previously reported isolate from a London Zoo chimpanzee. Phylogenetically distinct from the HBV-like sequences from gibbons, orangutans, and a gorilla so far reported, the Ch256 and Ch258 isolates would represent an indigenous chimpanzee HBV (tentatively ChHBV). A third chimpanzee (Ch195) had a 3212-nt genome, classifiable into the genotype E of HBV. Because HBV-E has been found mostly in Africans, Ch195 may have been infected from a human source in Africa. However, an inverse scenario is also possible: a spread of HBV-E might have occurred from chimpanzees to humans a long time ago in Africa. Analysis of the arginine-rich C-terminal region of the core protein, which is well conserved among mammalian hepadnaviruses, indicated that HBV-E/F and nonhuman primate hepadnaviruses are much closer than HBV-A/B/C/D to the hepadnaviruses of woodchuck and ground squirrel. Our results support an "ex-nonhuman primate" hypothesis for the origin of HBV.

摘要

乙型肝炎病毒(HBV)属于嗜肝DNA病毒科正嗜肝DNA病毒属。嗜肝DNA病毒在多种动物(鸭、鹭、土拨鼠、地松鼠和灵长类动物)中被发现,必然经历了漫长的进化史,其成员可能比目前已知的更多。黑猩猩可能也有自己的嗜肝DNA病毒,即便它可能与HBV非常相似。我们分析了来自三只黑猩猩(Pan troglodytes)的类HBV序列,它们很可能是在非洲野外生活期间感染的。两只黑猩猩(Ch256和Ch258)拥有长度为3182 nt的病毒基因组,前S1区域有33 nt的缺失,该序列无法归类为人HBV的六种基因型(A - F)中的任何一种,但与先前报道的一只伦敦动物园黑猩猩的分离株高度同源。与迄今报道的长臂猿、猩猩和一只大猩猩的类HBV序列在系统发育上不同,Ch256和Ch258分离株代表一种本土黑猩猩HBV(暂定为ChHBV)。第三只黑猩猩(Ch195)有一个3212 nt的基因组,可归类为HBV的E基因型。由于HBV - E大多在非洲人中发现,Ch195可能是从非洲的人类来源感染的。然而,相反的情况也有可能:很久以前在非洲,HBV - E可能从黑猩猩传播到了人类。对核心蛋白富含精氨酸的C末端区域的分析表明(该区域在哺乳动物嗜肝DNA病毒中高度保守),HBV - E/F和非人类灵长类嗜肝DNA病毒比HBV - A/B/C/D与土拨鼠和地松鼠的嗜肝DNA病毒更为接近。我们的结果支持HBV起源的“非人类灵长类起源”假说。

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