Seroepidemiological studies on hepatitis E and development of vaccine.

戊型肝炎类似于甲型肝炎，戊型肝炎病毒(HEV)通过粪便经口腔传播，只引起急性肝炎。这种戊型肝炎主要见于南亚，如印度、尼泊尔、缅甸、维古鲁自治区的中国等。1.建立动物模型，2.鉴定致病病毒，3.HEV基因组分子克隆，4.建立戊型肝炎诊断和血清流行病学研究试剂盒.5.疫苗研制.如果给恒河猴静脉注射足够量的病毒，就可以产生动物急性肝炎.此外，我们还可以从感染动物的胆汁中获得大量病毒。我们从胆汁中构建了lambda gt11基因文库，并对HEVRNA进行了免疫筛选。从3‘端获得了4个克隆，并对HEV全基因组进行了测序。我们还比较了缅甸克隆和中国克隆的序列。核酸序列同源性为93%。利用3‘末端多肽建立了抗-HEV试剂盒。我们在日本、中国和宫马进行了急性散发性肝炎筛查。我们发现在日本，我们观察到的输入性戊型肝炎病例很少，但在中国，甚至在北京和上海，几乎10%的急性散发性肝炎病例是由HEV引起的。我们用猴子进行了重组疫苗的药效试验。然而，我们的疫苗未能保护HEV感染。

Hepatitis E is similer to hepatitis A. Hepatitis E virus (HEV) is transmitted by fecal-oral route and only cause acute hepatitis. This hepatitis E is mainly observed in South-Asia, such as India, Nepal, Myanmar, Uiguru Autonomous Region of China. Attempt was made to 1. establish an animal model, 2. identify a causative virus, 3. molecular clone of HEV genomne, 4. establish an assay kit for diagnosis and sero-epidemiological study of hepatitis E. 5. Vaccine development.If we inoculate enough amount virus intravenously into rhesus monkeys we could produce acute hepatitis in animals. Also we could get large amount virus from the bile of the infected animals. We constructed lambda gt11 cDNA library from the bile and immunoscreened HEVRNA. We got 4 clones from 3'terminal and finally we sequenced whole genome of HEV. We also compared sequence of Burmese clone and Chinese clone. Homology was 93% in nucleic acid. We established assay kit for anti-HEV using peptide of 3'terminal region. We screened acute sporadic hepatitis in Japan, China and Miyanmar. We found in Japan, we observed very few imported cases of hepatitis E. However, in China, even Beijing and Shanghai, almost 10% of acute sporadic hepatitis cases were caused by HEV. We did efficacy experiment of recombinant vaccine using monkeys. However, we failed to protect HEV infection by our vaccine.