Molecular epidemiology of human herpes virus 8-relafed diseases in Japan and Asia

为了阐明日本和亚洲人类疱疹病毒8（HHV 8）相关疾病的分子流行病学，我们调查了卡波西肉瘤（KS）、多中心Castleman病（MCTD）和淋巴瘤组织中HHV 8及其亚型的频率。我们向台湾、韩国和泰国的病理学系寻求合作;我们于2000年访问了台湾的国立台湾大学和国立成功大学，于2001年访问了韩国的首尔国立大学、峨山医学中心和启明大学，并于2002年分别访问了泰国的清迈大学和玛希隆大学。福尔马林固定和石蜡包埋的组织切片，可用于研究，在台湾的19例KS，和10例KS，9例MCTD，和64例淋巴瘤在韩国。对于日本的组织，我们检查了12例KS和140例东京都驹目医院的淋巴瘤。对提取的DNA分别进行HHV 8-ORF 26巢式PCR、K-1VR 1-PCR和ORF 75-PCR扩增，并对扩增产物进行序列测定，结果19例台湾KS中18例（95%）、10例韩国KS中6例（60%）、HHV 8-ORF 26巢式PCR检测韩国MCTD 4例（44%），韩国淋巴瘤64例无一例。21例日本KS中21例（100%）和140例日本淋巴瘤中14例（10%）存在HHV 8-ORF 26。ORF 26和K1-VR 1两个系统的HHV 8亚型基本一致，但也有个别病例的亚型不同。ORF 75亚型与ORF 26亚型的比较也证实了部分日本KS中存在重组的证据。因此，频繁的重组表明，HHV 8已经在一个相对较小的群体中传播。

To clarify the molecular epidemiology of human herpes virus 8 (HHV8)-related diseases in Japan and Asia, we investigated the frequency of HHV8 and Its subtypes in the tissues of Kaposi sarcoma (KS), multicentric Castleman's disease (MCTD), and lymphomas. We asked cooperation to the Departments of Pathology, in Taiwan, Korea and Thailand; we visited National Taiwan University and National Cheng Kung University in Taiwan in 2000, Seoul National University, Asan Medical Center, and Keimyung University in Korea in 2001, and Chiang Mai University and Mahidol University in Thailand in 2002, respectively. The formalin-fixed and paraffin-embedded tissue sections, available for the study, were 19 cases of KS in Taiwan, and 10 cases of KS, 9 cases of MCTD, and 64 cases of lymphomas in Korea. For the tissues in Japan, we examined 12 cases of KS and 140 cases of lymphomasof Tokyo Metropolitan Komagome Hospital. The extracted DMA was subjected to the HHV8-ORF26 nested PCR, K-1VR1-PCR and ORF75-PCR, and then the amplicons were sequenced for the determination of subtypes.Positive PCR results were observed in 18 of 19 Taiwan KS (95%), 6 of 10 Korean KS (60%), 4 of Korean MCTD (44%) and none of 64 Korean lymphomas by HHV8-ORF26 nested PCR On the other hand, HHV8-ORF26 was observed in 21 of 21 Japanese KS (100%) and 14 of 140 Japanese lymphomas (10%).As for the subtypes of HHV8, according to the sequence polymorphism in ORF26 or K1-VR1, type C was predominant in Taiwan and Korea, whereas type A in Japan, suggesting the particular propagation of HHV8 in Japan.Sub-typing of HHV8 was nearly concordant between ORF26 and K1-VR1 systems, but there were several cases that showed different subtypes in each sample. The comparison of ORF75 subtype with ORF26 also demonstrated the evidence of recombination in some of Japanese KS. Thus frequent recombination suggests that HHV8 has propagated in a relatively small group.