Study of simian TT virus (s-TTV) infection and its pathogenesis to humans

最近，我们从非人类灵长类动物中分离出TTV，并将其命名为类人猿TTV （s-TTV）。为了调查人类中s-TTV的流行情况，我们用PCR法检测了日本健康人和肝病患者的血清中s-TTV DNA的存在。利用s-TTV基因组非翻译区设计的s-TTV特异性引物，采用巢式PCR法测定s-TTV DNA。200例健康成人中有3例（1.5%）检测到s-TTV DNA序列，48例无肝病婴儿中未检测到s-TTV DNA序列。另一方面，在287例日本肝病患者中有30例（10.5%）检测到s-TTV DNA。s-TTV合并乙型肝炎病毒和丙型肝炎病毒的患者分别占16.7%和30%，而单独s-TTV阳性的患者占53.3%。对20例患者的核苷酸序列分析证实，这些PCR产物来源于s-TTV基因组序列，与黑猩猩s-TTV原型的序列几乎有85%相同。系统发育分析表明，所有从人类分离的s-TTV与从人类分离的TTV有明显的区别。此外，s-TTV在人类和猿类中被划分为2种不同的基因型。结果表明，日本肝脏疾病患者中s-TTV感染率为10.5%。s-TTV从动物到人类的传播途径需要澄清。

Recently, we identified TTV isolates from nonhuman primates and named them simian TTV (s-TTV). To investigate the prevalence of s-TTV in humans, we examined sera from healthy individuals and patients with liver diseases in Japan for the presence of s-TTV DNA by PCR assay. s-TTV DNA was determined by nested PCR using s-TTV-specific primers designed from untranslated region of s-TTV genome. s-TTV DNA sequence was detected in 3 of 200 (1.5%) healthy adults but none of 48 infants without liver disease. On the other hand, s-TTV DNA was detected in 30 of 287 (10.5%) Japanese patients with liver disease. s-TTV coinfection with hepatitis B virus and hepatitis C virus were present in 16.7% and 30% of these patients, respectively, while 53.3% of patients were positive for s-TTV alone. Nucleotide sequence analyses in 20 patients confirmed that these PCR products were derived from s-TTV genome sequences and nearly 85% identical to those of s-TTV prototypes from chimpanzees. Phylogenetic analysis demonstrated that all s-TTV isolates from humans were distinguished clearly from the human TTV isolates. Furthermore, s-TTV in humans was classified into 2 different genotypes as well as simians. Our results indicate that generally 10.5% of Japanese patients with liver diseases were infected with s-TTV. The routes of s-TTV transmission from animal to human require clarification.