Clinico-molecular characteristics of hepatitis D virus infection prevalent in a small island named Miyako island of Japan

前言：丁型肝炎病毒(HDV)感染在日本很少见。在乙肝表面抗原(HBs)阳性的日本人中，HDV慢性感染率不到1.0%。然而，在日本冲绳县宫古岛的居民中观察到了很高的抗HDV流行率。本次调查试图揭示该岛居民中HDV感染的确切流行情况和所分离的HDV基因组的分子特征。患者和方法：1996年对宫古岛4728名居民进行了定期健康检查。EIA法检测4728例中，375例(7.9%)为HBs Ag阳性。放射免疫法检测抗-HDV阳性32例(8.5%)。对这32名受试者的血清进行了分析，以进行进一步的病毒调查。从每100微升血清中提取HDV RNA，用第一对nt695-718和nt873-896；第二对nt726-745和nt846-865进行套式RT-PCR。The Neste…结果：15例受试者中有10例(31.3%)扩增出HDV基因。将这7个HDV基因的核苷酸序列分为两大类。A组由4个基因组组成，B组由3个基因组组成。A组核苷酸同源性为94.6%~98.0%，B组核苷酸同源性为96.1%~98.1%，A组与B组核苷酸同源性为84%~88%。A组和B组与已报道的2株日本毒株的核苷酸同源性分别为92.1-98%和82.4-86%，与日本境外报道的毒株同源性分别为41.5-96.2%和41.0-86.2%。同源性分析表明，宫古岛分离株属于I型。结论：宫古岛HDV分离株属于I型，与日本宫古岛外分离株不同。基因分析表明，宫古岛的HDV可能与黎巴嫩、瑙鲁和南欧有亲缘关系。目前尚不清楚HDV感染在该岛流行的原因，但进一步的基因组研究将为我们提供高感染途径的线索和HDV基因组分子进化的有趣信息。较少

Introduction : Hepatitis delta virus (HDV) infection is rare in Japan. The chronic infection rate of HDV is less than 1.0% among hepatitis B surface antigen (HBsAg)-positive Japaneses. However, a high prevalence rate of anti-HDV has been observed among inhabitants of Miyako Island of Okinawa Prefecture in Japan. The present investigation attempted to reveal the precise prevalence of HDV infection among inhabitans of this island and molecular characteristics of the HDV genome isolated.Patients and Methods : An periodic health check was performed for 4,728 inhabitans of Miyako Island in 1996. HBsAg-positive subjects were 375 (7.9%) among 4,728 by EIA method. Anti-HDV was positive in 32 (8.5%) among these 365 subjects by RIA method. Sera from these 32 subjects were analyzed for the further viral investigation. HDV RNA was extracted from each 100 micro liter serum and served for nested RT-PCR using primer pairs (first nt 695-718 and nt 873-896 ; second nt 726-745 and nt 846-865). The neste … More d PCR products of 6 subjects were sequenced, followed by nucleotide homology investigation.Results : The nested PCR successfully amplified HDV cDNA in ten (31.3%) out of the 15 subjects. The nucleotide sequence of these seven HDV cDNA were classified into two major groups. One (A) group consisted of 4 genomes and the other (B) group consisted of 3 genomes. While nucleotide homology was 94.6-98.0% among Group A and 96.1%-98.1% among B, that between Group A and Group B was 84-88%. Nucleotide homology of Group A and B with the 2 previously reported Japanese isolates was 92.1-98% and 82.4-86%, respectively, The homology with the previously reported isolates outside Japan was 41.5-96.2% for Group A and 41.0-86.2% for Group B.Pylogenic analysis showed Miyako isolates were classified into genotype I.Conclusion : HDV isolates of Miyako island are classified into genotype I and their genotype differs from that of Japan outside Miyako island. Genetic analysis suggests that HDV in Miyako island may be related phylognically with Lebanon, Nauru, and South Europe. It is unclear why HDV infection is prevalent in the isolated island ; however, the further genome investigation will provide us a clue of the route of high infection and interesting informations of molecular evolution of HDV genomes. Less