GB virus C/hepatitis G virus infection in Indian blood donors and high-risk groups.

The hepatitis G virus (HGV) or GB virus C (GBV-C) was discovered in 1995 as a putative agent of post-transfusion, non-A-E hepatitis. The present study was carried out with the aim to find the prevalence of this virus among various subject groups at risk for parenteral transmission as well as in healthy control subjects both individually and along with other parenterally transmitted hepatitis viruses. Of the 402 subjects tested, 6.22% were positive for the HBsAg surface antigen, 7.21% were positive for HCV RNA while only 2.24% were seen to be carriers of the HGV/GBV-C RNA. All the HGV/GBV-C positive cases were either multi-transfused thalassaemic subjects or hemodialysis patients. None of the healthy control subjects showed presence of the virus. Seven of the HGV/GBV-C positive subjects showed co-infection with one or more additional virological markers. Also, of the 9 HGV/GBV-C positive subjects, 5 showed elevated ALT levels while 4 showed elevated alkaline phosphatase levels. Overall our findings seem to indicate that HGV infections generally are asymptomatic, transient and self-limiting and the virus does not seem to show a very high prevalence among the Indian population.     

Phylogenetic analysis of hepatitis GB virus type C/hepatitis G virus in Spanish patients with chronic hepatitis B or C virus infection.

The nucleotide sequence of hepatitis GB virus type C (HGBV-C)/hepatitis G virus (HGV) NS3/helicase and 5'-untranslated regions from 23 Spanish patients were analyzed to assign the HGV isolates one of the proposed HGBV-C/HGV genotypes. The analysis of the evolutionary distance frequency showed that the distances among all sequences in NS3/helicase region were distributed around a single peak of 0.20, suggesting that all included sequences belonged to the same HGBV-C/HGV genotype. By contrast, in the 5'-untranslated region, all the distances corresponding to our sequences and those of the HGBV-C/HGV types 2 and 3 were distributed around a major peak of 0.03. The remaining distances corresponding to the HGBV-C/HGV type 1 sequences were distributed around a minor peak of 0.11. The phylogenetic tree and pairwise comparison of evolutionary distances among the 5'-untranslated region of the infected patients and each HGBV-C/HGV genotype demonstrated that our HGBV-C/HGV isolates belonged to subtype 2a (17/23; 78%) and 2b (5/23; 22%). No relation was found between HGBV-C/HGV subtype and hepatitis B or C virus infection.     

GB virus C/Hepatitis G virus.

Hepatitis G virus (HGV) is a positive, single-strand RNA virus that has been classified in the family Flaviviridae. The 5'-untranslated region (UTR) of the HGV genome is lengthy and does not share any significant primary and secondary RNA structures with the 5'-UTR of hepatitis C virus (HCV). The internal ribosome entry site has extraordinarily weak activity. The HGV genome does not seem to encode a nucleocapside protein analogous to HCV. Blood-borne transmission is presumed to be the commonest mode of transmission of the virus. Current infection with HGV is diagnosed by detection of HGV RNA by the polymerase chain reaction (PCR), and past infection with HGV is detectable by testing anti-HGV E2. HGV is distributed worldwide, but its prevalence varies widely from one population to another. Although the prevalence of HGV in association with acute and chronic hepatitis is higher than that in the general population, further prospective studies are needed to demonstrate its relative significance in causing hepatitis and other disease. The major unresolved biological issue at the moment is its hepatotropsim and site of propagation. Recent progress demonstrates that HGV replicates in lymphocytes rather than hepatocytes. HGV may be pathogenic under special conditions, but does not influence carcinogenesis.     

Detection of GB virus C/hepatitis G virus RNA by reverse-transcription polymerase chain reaction.

Recently, a novel RNA virus, designated GB virus C or hepatitis G virus (GBV-C/HGV) has been identified which may possibly be associated with human hepatitis. In this study, the nucleotide sequences of the partial nonstructural 5 (NS5) gene of GBV-C/HGV derived from sera of eight Chinese patients were determined. The overall degree of nucleotide conservation and the existence of regional highly conserved sequences make this part of the genome suitable for the development of diagnostic reagents. On the basis of sequence analysis, two sets of oligonucleotide primers were designed to establish a nested polymerase chain reaction (PCR) for detection of GBV-C/HGV RNA. The efficacy of three PCR methods (first, one stage PCR, second, nested PCR with primers from the NS5 region designed according to the prototype sequence and the third, our newly developed PCR) was compared in 133 Chinese patients with liver disease. The positive rates of these three methods were 8.3%, 11.3% and 18.0% respectively. The specificity of our PCR detecting system was verified by sequencing and restriction fragment length polymorphism (RFLP). In conclusion, because of the heterogeneity and geographic distribution character of GBV-C/HGV, it is necessary to assess the sequence variation among Chinese patients infected with GBV-C/HGV. This may allow to identify GBV-C/HGV RNA with high sensitivity and specificity.     

Hepatitis C virus and GB virus C/hepatitis G virus viremia in Swedish blood donors with different alanine aminotransferase levels

BACKGROUND: Hepatitis C virus (HCV) is a known blood-borne hepatotropic virus for which antibody screening of blood donors is universally practiced. The newly identified GB virus C (GBV-C) and its strain variant hepatitis G virus (HGV) are of unknown pathogenic significance, and screening of blood donors for this agent has not yet been implemented. Polymerase chain reaction (PCR) is the most sensitive method for detecting HCV viremia and is the only method presently available for the diagnosis of GBV-C/HGV infection. STUDY DESIGN AND METHODS: RNA extracts of sera from 577 anti-HCV-negative blood donors (393 with elevated alanine aminotransferase [ALT] levels, 184 with normal ALT levels) were tested with nested PCR for HCV and GBV-C/HGV directed at the 5'-noncoding regions of the two viruses. RESULTS: One donor with elevated ALT was HCV PCR positive. This donor was anti-HCV negative when recruited to the study but subsequently developed anti- HCV. Of the 19 donors with GBV-C/HGV viremia in the series as a whole, 16 belonged to the group with elevated ALT levels and 3 to the group with normal ALT levels; the group difference in prevalence was nonsignificant (4.1% [16/393] vs. 1.6% [3/184; p = 0.20]). Phylogenetic analysis showed 16 of the GBV-C/HGV isolates to be classifiable as subtype 2a and three as subtype 2b. At follow-up 3 to 5 years later, 11 of 18 donors were still viremic. CONCLUSION: There was no significant difference in GBV-C/HGV viremia in the group with elevated ALT levels and the group with normal ALT levels. The frequency and subtype distribution in the present series were similar to those in other Western countries.     

Mechanisms of hepatitis C virus infection

Hepatitis C virus (HCV) is the major causative agent of chronic non-A, non-B hepatitis. The life cycle of HCV is largely unknown because a reliable culture system has not yet been established. HCV presumably binds to specific receptor(s) and enters cells through endocytosis, as do other members of Flaviviridae. The viral genome is translated into a precursor polyprotein after uncoating, and viral RNA is synthesized by a virus-encoded polymerase complex. Progeny viral particles are released into the luminal side of the endoplasmic reticulum and secreted from the cell after passage through the Golgi apparatus. Understanding the mechanisms of HCV infection is essential to the development of effective new therapies for chronic HCV infection. Several host membrane proteins have been identified as receptor candidates for HCV. Recent advances using pseudotype virus systems have provided information surrounding the initial steps of HCV infection. An HCV RNA replicon system has been useful for elucidating the replication mechanism of HCV. In this review, we summarize our current understanding of the mechanisms of HCV infection and discuss potential antiviral strategies against HCV infection.     

The prevalence of serum GB virus C/hepatitis G virus RNA and anti-E2 in Japanese children without a history of blood transfusion

The prevalence of serum GB virus C (GBV-C)/Hepatitis G virus (HGV) RNA and anti-E2 was investigated in Japanese children younger than 16 years of age without a history of blood transfusion and the family members of serum GBV-C/HGV RNA-positive children. The prevalences of serum GBV-C/HGV RNA and anti-E2 were 0.5% (5/1000) and 0% (0/330), respectively. Viral RNA was also detected in the mothers of all five GBV-C/HGV RNA-positive children and in two of their siblings. Sequence determinations indicated the likelihood of mother-to-infant transmission in all cases. The presence of the virus persisted for at least 10-18 months in all 5 children, without any appearance of anti-E2.     

Treatment of chronic hepatitis C virus infection

OBJECTIVE: To review the literature on the treatment of chronic hepatitis C virus (HCV) infection. DATA SOURCES: MEDLINE search (1986-December 1999) using key words such as HCV, hepatitis, non-A and non-B hepatitis, as well as terms regarding treatment during that time period. DATA SYNTHESIS: HCV infection was initially treated with interferon monotherapy, but only a minority of patients responded to long-term therapy. A higher rate of response in both interferon-na?ve patients and interferon-relapsers has been achieved by using the combination of interferon and ribavarin. Other treatment regimens including high-dose interferon protocols, ursodeoxycholic acid, amantadine, and nonsteroidal antiinflammatory drugs have been less promising. Many alternative therapies are being investigated. CONCLUSIONS: HCV infection is a major public health problem. It is now possible to achieve a cure in nearly 50% of the patients with this infection. Many additional therapies are being evaluated in order to achieve a higher cure rate.     

庚型肝炎病毒E区部分基因克隆及序列分析

目的 建立适合我国国情的HGV诊断方法及进一步研制预防HG的疫苗。方法 通过逆转录-套式-聚合酶链反应,从1例输血后丙肝患血清中扩增出768bp的庚型肝炎病毒cDNA序列,反应产物克隆进M13mpl8噬菌体,阳性克隆抽提单链以双脱氧终止法双向测定其序列。结果 所分离的HGVE区768bp的核苷酸与国内外已发表的4株HGV序列比较,同源性分别为：U44402 81．5％,U45966 82．8％,U36380 84．5％,U75356 95．8％;根据所测得的cDNA序列推导出其编码的氨基酸序列,在氨基酸水平上较4株HGV序列同源性分别为：U44402 87．7％,U45966 91．5％,U36380 94．1％,U75356 95．8％。结论 证实国内存在丙型肝炎与庚型肝炎病毒合并感染;此序列与中国株HGV同源性较高,与美国株HGV及西非株(GBV-C)同源性相对较低;推导出的氨基酸水平的同源性高于核苷酸水平;HGV E区较非结构区NS3、NS5及5’非编码区(5'UTR)的变异为大。     

输血传播病毒感染与丙型肝炎病毒感染的相互影响

目的了解输血传播病毒(TTV)与丙型肝炎病毒(HCV)重叠感染的发生率,探讨TTV感染与HCV感染的相互影响。方法采用酶联免疫吸附试验(ELISA)法检测血清中人类免疫缺陷病毒(HIV)、乙型肝炎病毒(HBV)、HCV、庚型肝炎病毒(HGV)及TTV标志物,应用巢式聚合酶链反应(n-PCR)技术检测血清TTV DNA,用速率法或终点法检测血清肝功能指标,用放射免疫法检测血清肝纤维化指标,用超声诊断仪检查肝胆脾形态及动态指标;应用SPSS 11.0软件分析比较肝功能检测结果、肝纤维化指标检测结果及肝脾形态和动态指标改变的差异。结果TTV/HCV重叠感染占TTV感染的69.6%(39/56),占HCV感染的61.9%(39/63)。TTV、HCV感染与TTV/HCV重叠感染肝功能检测结果差异有统计学意义(P<0.05);肝纤维化指标检测结果差异有统计学意义(P<0.05)。结论TTV/HCV重叠感染存在很高的发生率,感染者肝损程度较重,临床进程加快,有肝纤维化趋势。