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Association of human herpesvirus 6 (HHV-6) in hematological malignancies and vertical transmission of HHV-6 genome

人类疱疹病毒 6 (HHV-6) 与血液恶性肿瘤的关联及 HHV-6 基因组的垂直传播

基本信息

批准号：
11671002
负责人：
DAIBATA Masanori
金额：
$ 1.98万
依托单位：
Kochi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

1. Over the past 15 years three new human hepesviruses (HHV-6, HHV-7 and HHV-8) have been recognized and implicated as eliological agents of several human diseases. HHV-6 has been cited as a possible cause or as a modulating element of certain human lymphoproliferative disorders. We found two cases of lymphoma and ALL carrying chromosomally integrated HHV-6 genomes. To assess the possibility of chromosomal transmission of HHV-6 DNA, we looked for the viral genome in their families. In both cases, the HHV-6 genomes were detected in their offspring at the identical sites of viral integration of the patients. We propose a novel latent form for HHV-6, in which integrated HHV-6 genome can be chromosomally inherited.2.(1) Despite the genomic homology, and serological cross-reactivity between HHV-6 and HHV-7, evidence for the association of HHV-7 with lymphoproliferative disorders has been scarce. We searched for the HHV-7 genome in patients with lymphocytic leukemia. Sixty-one patients were enrolled : 33 adult ALL ; 15 childhood ALL ; and 13 CLL. HHV-7 genome was not found in any of our samples, suggesting that HHV-7 is unlikely to play a pathogenetic role in lymphocytic leukemia.(2) We evaluated the presence of four human herpesviruses (EBV, HHV-6, HHV-7 and HHV-8) in the specimens from 14 patients with primary ocular MALT lymphoma. EBV DNA were detected in 4 samples by PCR, and 4 cases were positive for HHV-6DNA. Neither HHV-7 nor HHV-8DNA could by detected. These findings suggested the possible involvement of EBV and HHV-6 in the pathogenesis of a subset of low-grade primary ocular lymphomas.(3) HHV-6 genome was detected in the brain lesions of progressive multifocal leukoencephalopathy (PML) developing in a lymphoma patient. HHV-6 is known to be reactivated during immunosuppression and can cause several fatal complications. We propose an association of HHV-6 with the pathogenesis of PML in immunocompromised hosts.

1.在过去的15年里，三种新的人类肝炎病毒(HHV-6、HHV-7和HHV-8)被认为是几种人类疾病的病原体。HHV-6被认为是某些人类淋巴增生性疾病的可能原因或调节因素。我们发现了两例淋巴瘤，均携带染色体整合的HHV-6基因组。为了评估HHV-6DNA通过染色体传播的可能性，我们寻找了他们家族中的病毒基因组。在这两个病例中，在他们的后代中，在患者病毒整合的相同位置检测到HHV-6基因组。我们提出了一种新的HHV-6潜伏形式，其中整合的HHV-6基因组可以在染色体上遗传。2。(1)尽管HHV-6和HHV-7之间存在基因组同源性和血清学交叉反应，但HHV-7与淋巴增殖性疾病相关的证据一直很少。我们在淋巴细胞白血病患者中搜索了HHV-7基因组。入选患者61例，成人ALL 33例，儿童ALL 15例，CLL 13例。在所有样本中均未发现HHV-7基因组，提示HHV-7在淋巴细胞性白血病中可能起致病作用。(2)我们检测了14例原发眼MALT淋巴瘤患者标本中四种人类疱疹病毒(EBV、HHV-6、HHV-7和HHV-8)。4例标本经聚合酶链式反应检测出EB病毒DNA，其中4例HHV-6DNA阳性。HHV-7和HHV-8DNA均未检出。这些发现提示EBV和HHV-6可能参与了一组低度恶性原发眼淋巴瘤的发病机制。(3)在1例淋巴瘤患者发生的进行性多灶性白质脑病(PML)的脑部病变中检测到HHV-6基因组。众所周知，HHV-6在免疫抑制期间会重新激活，可能会导致几种致命的并发症。我们建议HHV-6与免疫受损宿主中PML的发病机制有关。