中国河南TTV分离株部分基因的克隆及序列测定

TTV是1997年底由日本学者首先发现的一种单链DNA病毒。随后的研究表明它与转氨酶异常有密切关系,并认为是一种与输血后肝炎有关的病毒。今年2月军事医学科学院的研究者首先证实我国人群中存在这种病毒的广泛感染。河南省历来是肝炎高发的地区之一,以往的研究表明存在大量的非甲非戊型肝炎病人和病原不明的输血后肝炎病例。为了证实我省是否存在TTV的感染以及了解TTV的感染状况,我们检测了部分非甲非戊型肝炎病人和献血员的标本并对河南株TTV的部     

输血传播病毒的研究进展

输血传播病毒(TTV)是日本首次发现的与转氨酶异常升高相关的病毒,是一种可能引起输血后肝炎的新的DNA病毒,从而引起了世界各国学者的关注,分别对其DNA的基因结构、基因分型、传播途径、流行病学调查及其致病机理进行了广泛的研究,但尚存很多争议。本文就TTV的基因结构、传播途径及致病性等方面的最新研究成果作一综述。     

人类肝炎相关病毒——TT病毒研究现状

TT病毒(TTV)是1997年底新发现的无包膜、单链DNA肝炎相关病毒,可能属于微小病毒科。在暴发型肝炎病人、慢性不明原因肝病病人、经血感染高危人群、甚至健康献血者中均可检出TTV DNA。研究发现,TTV既可通过非肠道途径传播,也可通过粪-口途径传播,其核酸序列变异较大,存在不同的基因型。我国是病毒性肝炎高发区,有必要对TTV进行深入的研究。本文介绍TTV的发现、特性及分类地位、检测方法、基因分型及其传播途径和致病性。     

HBsAg阳性肝病患者血清TTV抗体的检测

输血传播病毒(TTV)最早由Nishizawa等于1997年从1例不明原因的输血后非甲～庚型肝炎患者血清中发现。尽管在许多原因不明的重症肝炎和不明原因的ALT升高患者血清和肝组织中能够检测到TTV DNA，但关于TTV的致病性和在其他病毒性肝炎(甲～庚型)中的作用以及TTV是     

供血者和血制品中一种新DNA病毒(TTV)的检测

背景:一种新发现的DNA病毒,即输血传播病毒(TTV),被认为能导致输血后肝炎。作者调查了英国供血者TTV病毒血症的发病率及其污染如凝血因子Ⅷ和Ⅸ之类的血制品的程度,也调查了在原因不明的爆发型肝衰(FHF)TTV可能的病原作用。疗法:作者从供者和FHF患者的血浆或血液以及从血制品(凝血因子Ⅷ和Ⅸ浓缩物,免疫球蛋白制品)中提取DNA。通过PCR检测TTV,所用引物来自TTV染色体组的保守区。发现:在1000位无报酬常规献血者里有19位(1.9％)被检测患者TTV病毒血症。与感染肝炎病毒和其它肠道传染病毒的供血者     

输血传播SEN病毒研究进展

通过筛查献血者乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV),输血后肝炎的发生率明显降低,但仍有部分输血后不明原因的肝炎发生。1995年分离出的庚型肝炎病毒(HGV)和1997年分离出的输血传播病毒(TTV)一度被认为与输血后非甲非戊型肝炎发生有关,但随后的研究发现在正常人群中存在一定比例的HGV和TTV感染,其致病性值得怀疑。2000年,意大利学者Primi等[1]从1例静脉吸毒者的HIV阳性血清中分离出一种新的可经输血传播病毒———SEN病毒(SENV)。SENV一经发现即被各国学者所重视,有关SENV的基因结构、检测方法、流行病学与肝炎的相关性等…     

丙型和戊型肝炎实验室诊断进展

近已确认非甲非乙型肝炎由两种不同的特异性病毒引起,并建立了特异性诊断方法,结合流行病学和临床特点,已把肠道外传播的非甲非乙型肝炎命名为丙型肝炎(HC),而把肠道传播的非甲非乙型肝炎称为戊型肝炎(HE)。这样按病毒不同,病毒性肝炎有甲、乙、丙、丁、戊型五种。HC 的传播途径主要是经血传播。即使严格筛选HBsAg 携带者,输血后肝炎发生率仍高达10～15%,且其中95%为HC。HC 发     

TT病毒研究进展与存在问题回顾

1997年Nishizawa等[1]从日本一名输血后非甲非戊型肝炎病人克隆到1个500bp的片段(N22),证实其与输血后肝炎高度相关,并把该基因片段可能代表的病毒以病人名字命名为TT病毒(TTvirus,TTV)。同年,日本科学家完成TTV全基因的测定。我国1998年6月由中国军事医学科学院首次分离出中国...     

33例TTV感染的血清病原学及临床分析

1997年Nishizawa等[1]从1例输血后肝炎病人血清中分离到一种新的DNA病毒,称为经血传播病毒（transfuslontransmittedvirus,TTV）。初步研究提示,ThV可经血传播,可能与部分非甲一庚型肝炎相关［'］。为了解ThV感染的临床特征,我们对深圳地区33例TTV感染者进行了血清病原学及临床分析,并对TTV的传播途径及其致病性作一探讨。l材料与方法1．l研究对象本组33例为1995年6月～1998年7月深圳市东湖医院的住院病人,其中男23例,女10例,年龄23～74岁,部分病例取原保留血清进行回顾性调查。所有病人诊断符合1995年第五次全国传染病与…     

应用聚合酶链反应检测南京地区TT病毒感染

目的：了解南京地区TT病毒感染情况。方法：采用巢式PCR方法检测血清标本中TTV－DNA。结果：163例病毒性肝炎患者血清标本中,TTV－DNA总检出率为21.5％（35／163）,其中甲型肝炎13.3％（4／30）,乙型肝炎21.3％（16／75）,丙型肝炎20.0％（3／15）,戊型肝炎5.3％（1／19）,非甲－庚型肝炎45.8％（11／24）。结论：南京地区存在TTV感染,TTV是导致非甲－庚型肝炎的重要病因,TTV可能存在非血源性传播途径。     

Clinical feature of TTV-related hepatitis]

It has been clarified that hepatitis G/GB virus-C is the minor cause of acute and chronic non-A-E hepatitis. But there exist non-A-E viral hepatitis patients. Recently, one of non-A-E hepatitis associated virus was identified and the new virus was named TT virus. We highly detected TT virus in the serum of hepatitis patients. TT virus were reported to be detected 1-37% of the general population in the world. TT virus may account for only a minor part of acute non-A-E hepatitis in Japan. However, whether TT virus infection really causes severe acute hepatitis is required to be elucidated.     

Roles of TT virus infection in various types of chronic hepatitis

An unenveloped single-stranded virus, which might be a causative agent for posttransfusion non-A-G hepatitis, was recently found and named "TT virus" (TTV). There is still controversy over the role of TTV in chronic hepatitis. Therefore, we have examined the prevalence of TTV in various types of chronic hepatitis in Japan. TTV DNA was detected in 11 of 40 patients (27.5%) with non-B, non-C chronic hepatitis, 13 of 46 patients (28.3%) with type B chronic hepatitis, 21 of 55 patients (38.2%) with type C chronic hepatitis, and 41 of 131 subjects (31.3%) with normal liver function tests. The positivity rate for TTV DNA tended to increase with age. The detection rate did not differ statistically between non-B, non-C chronic hepatitis and type B or type C chronic hepatitis, or normal subjects. The distribution of TTV genotypes was not significantly different among them. Clinical characteristics of the chronic illness were similar for patients with or without TTV in all hepatitis groups. The etiologic role of TTV in chronic hepatitis is not confirmed from the statistical and clinical standpoint.     

Nucleic acid testing for emerging viral infections

The development of new technologies leads to the discovery of new viruses. For each of these new infectious agents, relevance to transfusion, including transmissibility by transfusion, pathogenicity, prevalence in blood donors, persistence and the availability of screening assays needs to be assessed. Since 1995, one virus and a new family of viruses have been identified. GB virus-C/hepatitis G virus (GBV-C/HGV), a flavi virus with some homology with and epidemiological features of HCV, is not related to post-transfusion hepatitis but seems to positively interfere with human immunodeficiency virus replication. Human circoviruses include TT virus (TTV) and SEN-V. Both are highly variable, constituting a large family of distantly related viruses. They appear ubiquitous, infecting humans very early in life and are largely persistent. No clinical symptoms or pathogenicity is associated with TTV, but SEN-V might be associated with some non-A-E post-transfusion hepatitis. Parvovirus B19 has been known for many years, but its transmission to recipients of plasma derivatives despite viral inactivation raised the issue of screening plasma pools by nucleic acid testing. Most fractionators quantify B19 DNA in plasma pools to ensure a viral load of <10(4) IU mL-1.     

Infection by an unenveloped DNA virus associated with non-A to -G hepatitis in Japanese blood donors with or without elevated ALT levels

BACKGROUND: An unenveloped, single-stranded DNA virus named TT virus has been found in association with elevated alanine aminotransferase (ALT) levels in recipients of transfusions and has been detected frequently in patients with acute or chronic hepatitis of non-A to -G etiology in Japan. DNA of the TT virus was searched for in blood donors with or without elevated ALT levels. STUDY DESIGN AND METHODS: A total of 861 blood donors without previous transfusions and who were negative for markers of hepatitis B or C virus infection were tested. DNA of the TT virus was detected by polymerize chain reaction with hemi-nested primers. RESULTS: TT virus DNA was detected in 62 of 280 (22.1% [95% CI: 18.1-26.6]) donors with elevated ALT levels (mean +/- SD, 89.3 +/- 36.4 U/L; range, 61-301 U/L), which is significantly more frequently (p<0.02) than its detection in 91 of 581 (15.7% [95% CI: 13.2-18.4]) donors with normal ALT (< or = 45 U/L).The frequency of TT virus DNA increased with age, in donors with and without elevated ALT. CONCLUSION: The detection of TT virus DNA, at a frequency higher in donors with elevated ALT than in those without, strengthens the association of TT virus with non-A to -G hepatitis.     

Pathogenic significance and organic virus levels in patients infected with TT virus.

Previous reports documented the recovery of a DNA virus from a patient with posttransfusion non-A-G hepatitis and named TT virus (TTV). Although the virus was initially detected as a causative agent of hepatitis, there is doubt about its pathogenicity. The aim of this study was to clarify the relationship between TTV and liver diseases. Histopathological examination of liver biopsies from 14 patients with TTV genotype 1 positive non-B, non-C and non-G chronic hepatitis showed mild fibrosis and periportal/piecemeal necrosis. Using the real-time detection (RTD)-PCR method, we found that TTV DNA levels of genotype 1 in liver samples from 3 such patients were 100- to 1,000-fold higher than those in the paired serum samples. Further investigation using various tissues from 2 autopsies of patients with hepatitis C with hepatocellular carcinoma revealed that the concentrations of TTV DNA in the liver were also higher than in serum samples. However, the highest TTV DNA concentrations in these 2 autopsies were found in the lung and bone marrow, respectively. Our results suggest that TTV may replicate in various tissues including the liver and may cause only mild liver damage.     

The prevalence of TTV infection and the route of TTV transmission in hemodialysis patients--compared with HCV infection]

Recently a novel virus named TT virus (TTV), associated with posttransfusion hepatitis, was isolated. The prevalence of TTV infection and the route of TTV transmission in HD units was investigated. TTV was detected in 51.3% of patients on HD (59/115), as compared with 16.5% of healthy blood donors (15/91). The prevalence rate of TTV in the patients without history of blood transfusion was similarly high (51.6%), compared with that of those with history of blood transfusion (51.2%). The prevalence rate of TTV did not differ according to the duration of HD. These suggest that the risk of TTV infection is very high in HD units and there is another major route of TTV transmission than blood transfusion.     

Prevalence of TT virus infection and viral integration in human hepatocellular carcinoma]

In 1997, Nishizawa et al cloned a novel DNA virus designated as TT virus (TTV) from a patient with post-transfusion hepatitis and this virus is being thought to be a new hepatitis virus. Approximately 5 to 10% of hepatocellular carcinomas (HCCs) in Japan occurs in hepatitis B virus-negative and hepatitis C virus-negative (NBNC) patients. In order to study the possible role of TTV in hepatocarcinogenesis, we studied the prevalence of the TTV DNA in liver tissue of HCC patients. As a result, TTV was shown not to be specific for NBNC HCC and TTV integration into host DNA was not detected in any HCC patient by Southern blotting.     

Detection of TT virus DNA in patients with non-A to G liver diseases]

A novel single-stranded DNA virus, TT virus(TTV), has been reported recently. We detected TTV viral sequences by polymerase chain reaction using primers derived from nucleotide sequences of ORF1 and the 5' noncoding region of ORF2. Using primers of the 5' noncoding region, TTV DNA was detected in 21 of 25(84%) healthy individuals, suggesting that most TTV strains detected by these primers are almost harmless. In contrast, using primers of ORF1, which detect genotype 1a TTV that was reported to be a causative agent of posttransfusion hepatitis, TTV DNA was detected in only 3 of 25 healthy subjects and 3 of 27 acute and 9 of 72(12%) chronic non-A to G hepatitis patients. Whether these TTV strains actually cause hepatitis remains to be determined.     

The association of TTV genetic variant with liver disease]

TT virus (TTV), a novel DNA virus, has been reported in non-A to non-G posttransfusion hepatitis patients. Among 61 Japanese patients with liver diseases of non-B and non-C etiology, TTV DNA was detected in 15(25%) patients. The N22 region of TTV was sequenced and compared with the published sequence. Four genetic groups corresponding to G1a, G1b, G2 and G4 were formed. TTV was detected persistently regardless of its genotype/subtype. However, G2 and G4 contained 10 to 100 folds lower in titer than G1. Co-existing multiple mutants and subtypes were identified in one case. Since changes of TTV DNA titer and appearance of deduced amino acid substitution was not linked to ALT levels, the association of TTV to chronic liver diseases seemed low.     

2000年2月份全国疾病监测点35种法定传染病疫情动态分析

本研究通过对我国部分地区的自然人群和非甲非戊型肝炎病人进行HGV和TTV感染的分子流行病学研究,探讨这两种病毒在我国肝炎发病尤其是在非甲非戊型肝炎中的作用和地位.用建立的PCR方法检测血清标本中的HGV RNA和TTV DNA,对调查的自然人群和非甲非戊型肝炎病人血清标本进行检测.HGV RNA采用反转录PCR(RT-PCR)检测,TTV DNA则采用巢式PCR方法检测.结果表明,HGV在自然人群中HGV RNA携带率为0.6%～1.1%,TTV的病原携带率则高达7.1%～12.4%;非甲非戊型肝炎病人中HGV和TTV的阳性率分别为7.9%和28.1%.在所检测的非甲非戊肝炎病人中HGV和TTV的总感染率为35.9%(包括了HGV和TTV的混合感染).因此,HGV在自然人群中感染率低,而且在非甲非戊型肝炎病人中约为10%的病人是由HGV的感染所致,HGV不是非甲非戊型肝炎病人的主要病因.TTV DNA在自然人群中的携带率约为10%,类似于HBV DNA的携带率.虽然在非甲非戊型肝炎病人中TTV DNA的阳性率为28%,但仍然有高达60%的病人病因不明,TTV感染也不是非甲非戊型肝炎病人的主要致病病原.