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Objective: Human pegivirus (HPgV-1, GBV-C) is classified within the Pegivirus genus of the Flaviviriade family. The natural history of HPgV-1 infection is still unclear, however, the main route of viral transmission seems to be the parenteral one. The detection of HPgV-1 viremia in blood donors without parenteral exposure demonstrates that other routes of HPgV-1 transmission might also exist. The objective of the present study was to evaluate the prevalence of HPgV-1 RNA and circulating genotypes among blood donors from a intra-hospital Hemotherapy Service localized in the Santa Maria city, central part of the Rio Grande do Sul State in the extreme South of Brazil., Methods: Blood samples were obtained from 373 volunteer blood donors and tested for the presence of HPgV-1 RNA. All positive for RNA samples were submitted to sequencing and phylogenetic analysis., Results: The prevalence of the HPgV-1 RNA was 5.9% (22/373). The performed phylogenetic analysis demonstrated a predominant detection of genotype 2 with its both subgenotype forms (95.5% of all isolates i.e 54.5% belonging to subgenotype 2 A and 40.9% belonging to subgenotype 2B). Only one sequence was classified as genotype 3 (1/22, 4.5%)., Conclusions: Our study demonstrates the circulation pattern and genotypes of HPgV-1 among volunteer blood donors of South Brazil, and adds to the global knowledge of the natural history and possible transmission routes of this viral agent with putative impact on the area of hemotherapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Hepatitis G virus (HGV) infection appears to be common in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to investigate the prevalence of HCV/HGV in patients with chronic hepatitis C (CHC) in Pakistan and to look for possible associations with various clinical and histopathological changes in HCV/HGV coinfection and HCV infection., Patients and Methods: The present study included 136 patients. Clinical, biochemical, virological and histological findings were compared between patients coinfected with HCV/HGV and patients with HCV alone., Results: Of the 136 patients with CHC, 16 (11.76%) were coinfected with HCV/HGV. The mean age of coinfected patients was lower than in patients with HCV alone. HCV/HGV coinfected patients did not show significant differences in sex, clinical presentation, biochemical markers, and liver fibrosis as compared to those with HCV infection. Only the mean values of platelets count, mean corpuscular hemoglobin (MCH), and MCH concentration markers were significantly different in HCV/HGV coinfected patients as compare to patients with HCV alone., Conclusion: It was found that 11.76% of patients with CHC in Pakistan were associated with HCV/HGV coinfection. No significant differences were observed in clinical and histological features except for platelets count, MCH, and MCH concentration markers between HCV and HGV coinfected patients in comparison with HCV-infected patients.

The article considers methods of laboratory diagnostic of parenteral viral hepatitis. The approaches ensuring single-valued differentiation of infected patients are determined. The various methods of evaluation of activity of infection process are presented. The algorithm of complex laboratory analysis concerning presence of parenteral viral hepatitis (B, C, D, G, TT, SEN) was proposed to ensure maximal informative minimum of laboratory analyses permitting fast and single-valued interpretation of received diagnostic data.

Introduction: Co-infection with GB virus C (GBV-C) in patients infected with human immunodeficiency virus 1 (HIV-1) has been associated with prolonged survival. The aim of this study was to evaluate the prevalence of GBV-C infection among HIV-1-infected patients in Venezuela, and to determine the effects of the co-infection on the levels of relevant cytokines., Methodology: Plasma samples were collected from 270 HIV-1-seronegative and 255 HIV-1-seropositive individuals. GBV-C infection was determined by RT-PCR of the NS5 region and genotyped by sequence analysis of the 5´UTR region. HIV-1 strains were characterized by sequence analysis of pol, vif, env, and nef genes. Selected cytokines were evaluated by ELISA., Results: Ninety-seven of 525 (18.5%) plasma samples tested positive for GBV-C RNA. A significantly higher prevalence of GBV-C was found among HIV-1 patients compared to HIV-1-seronegative individuals (67/255, 26% versus 30/270, 11%; p < 0.001). Statistical difference was observed in the viral load between HIV-1+GBV-C+ and HIV-1+GBV-C- (p = 0.014), although no differences in CD4+ cell counts were found between both groups. TNFα concentration was higher in HIV-1+GBV-C- than in HIV-1+GBV-C+ patients (25.9 pg/mL versus 17.3 pg/mL; p = 0.02); RANTES expression levels were more variable in GBV-C co-infected patients and more frequently elevated in HIV-1 mono-infected patients compared to patients co-infected with GBV-C., Conclusions: The previously observed beneficial effect of co-infection with HIV-1 and GBV-C on disease progression is complex and might be due in part to a change in the cytokine environment. More studies are required to understand the interaction between both viruses.

Human pegivirus (HPgV; previously called GB virus C/hepatitis G virus) has limited pathogenicity, despite causing persistent infection, and is associated with prolonged survival in human immunodeficiency virus-infected individuals. Although HPgV RNA is found in and produced by T- and B-lymphocytes, the primary permissive cell type(s) are unknown. We quantified HPgV RNA in highly purified CD4(+) and CD8(+) T-cells, including naïve, central memory and effector memory populations, and in B-cells (CD19(+)), NK cells (CD56(+)) and monocytes (CD14(+)) using real-time reverse transcription-PCR. Single-genome sequencing was performed on viruses within individual cell types to estimate genetic diversity among cell populations. HPgV RNA was present in CD4(+) and CD8(+) T-lymphocytes (nine of nine subjects), B-lymphocytes (seven of ten subjects), NK cells and monocytes (both four of five). HPgV RNA levels were higher in naïve (CD45RA(+)) CD4(+) cells than in central memory and effector memory cells (P<0.01). HPgV sequences were highly conserved among subjects (0.117±0.02 substitutions per site; range 0.58-0.14) and within subjects (0.006±0.003 substitutions per site; range 0.006-0.010). The non-synonymous/synonymous substitution ratio was 0.07, suggesting a low selective pressure. Carboxyfluorescein succinimidyl ester (CFSE)-labelled HPgV RNA-containing particles precipitated by a commercial exosome isolation reagent delivered CSFE to uninfected monocytes, NK cells and T- and B-lymphocytes, and HPgV RNA was transferred to PBMCs with evidence of subsequent virus replication. Thus, HPgV RNA-containing serum particles including microvesicles may contribute to delivery of HPgV to PBMCs in vivo, explaining the apparent broad tropism of this persistent human RNA virus.

Hepatitis C virus (HCV) and GB virus type C (GBV-C) are associated with impaired T cell function despite the fact that HCV replicates in hepatocytes and GBV-C in a small proportion of lymphocytes. Recently, we showed that HCV and GBV-C E2-envelope proteins reduce T cell activation via the T cell receptor (TCR) by competing for phosphorylation with a critical kinase in the TCR signaling cascade (Lck). E2 interfered with TCR signaling in E2 expressing cells and in bystander cells. The bystander effect was mediated by virus particles and extracellular microvesicular particles (exosomes). Multiple kinase substrate sites are predicted to reside on viral structural proteins and based on bioinformatic predictions, many RNA virus pathogens may interfere with TCR signaling via a similar mechanism. Identification of T cell inhibitory effects of virus structural proteins may provide novel approaches to enhance the immunogenicity and memory of viral vaccines.

We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.

A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms. HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C), since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments. GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells. Therefore, GBV-C shares partly the same ecological niche with HIV-1. In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry. In this study we investigated the underlying mechanism. Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor. Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41. In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120. This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface. Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors.

Double-negative T cells (DNTCs; ie, CD3(+)CD4(-)CD8(-) T cells) play a role in limiting chronic immune activation. GB virus C (GBV-C) infection is associated with reduced T-cell activation in human immunodeficiency virus (HIV)-infected individuals. T-cell activation and DNTCs were measured in HIV-infected subjects with a nondetectable HIV load. GBV-C-viremic subjects had significantly reduced CD4(+) and CD8(+) T-cell activation (P = .003 and .034, respectively) and significantly increased DNTCs (P = .038), compared with nonviremic subjects. GBV-C load correlated with DNTC percentage (P = .004). Thus, GBV-C infection is associated with an increase in DNTCs, which may contribute to reduced immune activation during HIV infection.

GB virus C (GBV-C) is a member of the Flaviviridae family and the most closely related human virus to HCV. However, GBV-C does not replicate in hepatocytes, but rather in lymphocytes. GBV-C has a worldwide distribution and is transmitted sexually, parenterally and through mother-to-child transmission. Thus, co-infection with HCV and HIV is common. Until now, no human disease has been associated with GBV-C infection. However, there are several reports of a beneficial effect of GBV-C on HIV disease progression in vivo. Different mechanisms to explain these observations have been proposed, including modification of antiviral cytokine production, HIV co-receptor expression, direct inhibition of HIV-1 entry, T-cell activation and Fas-mediated apoptosis. Further understanding of these mechanisms may open new strategies for the treatment of HIV/AIDS.

Background: GB virus C (GBV-C) infection is transmitted by blood exposure and associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients., Methods: We used a limited-access database from the National Heart Lung and Blood Institute's Viral Activation Transfusion Study, a randomized controlled trial of leukoreduced versus nonleukoreduced transfusions received by HIV-infected, transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers in pretransfusion and posttransfusion samples. We estimated the risk of acquiring GBV-C RNA and predictors of GBV-C acquisition, using pooled logistic regression., Results: GBV-C RNA was detected ≤120 days following the first transfusion in 22 (7.5%) of 294 subjects who were GBV-C negative before transfusion. The risk of GBV-C RNA acquisition increased with each unit transfused (odds ratio, 1.09; 95% confidence interval, 1.06-1.11). Lower baseline HIV load and use of antiretroviral therapy were associated with subsequent GBV-C RNA acquisition, after control for units of blood transfused. Leukoreduced status of transfused units was not associated with GBV-C transmission., Conclusions: Blood transfusion is associated with a significant risk of GBV-C acquisition among HIV-infected patients. Transmission of GBV-C by blood transfusion was inversely related to HIV load.

GBV-C infection is associated with prolonged survival and with reduced T cell activation in HIV-infected subjects not receiving combination antiretroviral therapy (cART). The relationship between GBV-C and T cell activation in HIV-infected subjects was examined. HIV-infected subjects on cART with non-detectable HIV viral load (VL) or cART naïve subjects were studied. GBV-C VL and HIV VL were determined. Cell surface markers of activation (CD38(+)/HLA-DR(+)), proliferation (Ki-67+), and HIV entry co-receptor expression (CCR5+ and CXCR4+) on total CD4+ and CD8+ T cells, and on naïve, central memory (CM), effector memory (EM), and effector CD4+ and CD8+ subpopulations were measured by flow cytometry. In subjects with suppressed HIV VL, GBV-C was consistently associated with reduced activation in naïve, CM, EM, and effector CD4+ cells. GBV-C was associated with reduced CD4+ and CD8+ T cell surface expression of activation and proliferation markers, independent of HIV VL classification. GBV-C was also associated with higher proportions of naïve CD4+ and CD8+ T cells, and with lower proportions of EM CD4+ and CD8+ T cells. In conclusion, GBV-C infection was associated with reduced activation of CD4+ and CD8+ T cells in both HIV viremic and HIV RNA suppressed patients. Those with GBV-C infection demonstrated an increased proportion of naive T cells and a reduction in T cell activation and proliferation independent of HIV VL classification, including those with suppressed HIV VL on cART. Since HIV pathogenesis is thought to be accelerated by T cell activation, these results may contribute to prolonged survival among HIV infected individuals co-infected with GBV-C. Furthermore, since cART therapy does not reduce T cell activation to levels seen in HIV-uninfected people, GBV-C infection may be beneficial for HIV-related diseases in those effectively treated with anti-HIV therapy.

Background: GB virus C (GBV-C) coinfection is associated with reduced immune activation and a block in CD4(+) T-cell proliferation following interleukin-2 (IL-2) therapy in HIV-infected individuals. We examined peripheral blood mononuclear cells (PBMCs) from HIV-infected subjects with and without GBV-C viraemia to determine if GBV-C correlated with reactivation of latent HIV, T-cell proliferation or T-cell survival following in vitro activation with phytohaemagglutinin A and IL-2 (PHA/IL-2)., Methods: HIV-infected subjects whose HIV viral load was suppressed on combination antiretroviral therapy (cART) for >6 months were studied. PBMCs were cultured with and without PHA/IL-2 and monitored for HIV reactivation, proliferation and survival. GBV-C viraemia and in vitro replication were detected by real-time RT-PCR. HIV reactivation was determined by measuring HIV p24 antigen in culture supernatants. Proliferation was measured by counting viable cells and survival measured by flow cytometry., Results: Of 49 HIV-infected individuals, 26 had GBV-C viraemia. Significantly less HIV reactivation and PBMC proliferation following in vitro activation with PHA/IL-2 was observed in samples from GBV-C viraemic subjects compared with non-viraemic controls. Following 5 weeks in culture, GBV-C replication was associated with preservation of CD4(+) and CD8(+) T-cells compared with non-viraemic controls., Conclusions: GBV-C appears to inhibit immune activation and IL-2 signalling pathways, which might contribute to a reduction in reactivation of latent HIV from cellular reservoirs. In addition, GBV-C viraemia was associated with a reduction in activation-induced T-cell death. GBV-C-associated T-cell effects could contribute to the observed protective effect of GBV-C coinfection in HIV-infected individuals.

GB virus C (GBV-C) is prevalent globally and particularly among individuals at risk of parental exposures. Based on genetic diversity, this virus is now classified into six genotypes and many subtypes with distinct geographical distribution. In this study, 120 Injecting Drug Users (IDUs) were recruited from Yunnan province, China. Among them, 43 (35.8%) were positive for GBV-C RNA, 70 (58.3%) and 103 (85.8%) sero-positive for HIV-1 and HCV respectively. This revealed 18.3% of IDUs having GBV-C/HIV/HCV triple infection, which is significantly higher than 7.5% of GBV-C/HIV-1 and 10% of GBV-C/HCV dual infection rates (P<0.05). Based on 5'UTR sequences, the identified 43 viral isolates can be classified into three phylogenetic groups: one (2.3%) and two (4.7%) belonged to genotype 3 and 4, respectively, and the remaining 40 (93%) formed a new group with 97% of bootstrap support. This new GBV-C group was further confirmed by characterizing the E2 region and full-length genome sequences. Analysis of 187 nt 5'UTR sequence showed three previous reported isolates from Southeast Asia were re-classified into this new group. It implies they have the same origin with strains from Yunnan. Although we provisionally assigned this new group as GBV-C genotype 7, a simpler five groups of GBV-C nomenclature is recommended. Genotype 4, 6 and the newly designated genotype 7 could be reclassified as one group, which may represent a single GBV-C genotype. The classification of the other four groups was corresponding to that of previous reported genotype 1, 2, 3 and 5. Furthermore, the diversity of amino acid sequence in the E2 region was analyzed. The inhibitory effect of GBV-C genotype 7 on HIV-1 cell entry could be deduced. Since GBV-C may have a beneficial effect on AIDS disease progression and interact with HCV during co-infection, this finding may raise interests in future studies on this virus that was previously thought to be a "non-pathogenic virus".

Hepatitis G virus (HGV) or GB-virus type C (GBV-C) is distributed globally and is present in the volunteer blood donor population. For epidemiological studies, HGV is of interest in hemodialysis patients who are at risk of parenterally transmitted infections. The role of HGV in producing illness and hepatic disease has yet to be determined. A review of literature was performed in 2009 to summarize scientific reports on epidemiology and pathogenesis of the HGV infection and its exposure through hemodialysis.

We investigated whether there was an association between GBV-C viremia and the development of non-Hodgkin lymphoma (NHL) in 553 NHL cases and 438 controls from British Columbia, Canada. Cases were aged 20-79, diagnosed between March 2000 and February 2004, and resident in Greater Vancouver or Victoria. Cases and controls were tested for GBV-C RNA by RT-PCR and positive samples were genotyped. Overall, GBV-C RNA was detected in 4.5% of NHL cases vs. 1.8% of controls [adjusted odds ratio (OR) = 2.72, 95% confidence interval (CI) = 1.22-6.69]. The association between GBV-C RNA detection and NHL remained even after individuals with a history of prior transfusion, injection drug use and hepatitis C virus sero-positivity were excluded. GBV-C viremia showed the strongest association with diffuse large B cell lymphoma (adjusted OR = 5.18, 95% CI = 2.06-13.71). Genotyping was performed on 29/33 GBV-C RNA positive individuals; genotypes 2a (n = 22); 2b (n = 5) and 3 (n = 2) were identified, consistent with the distribution of genotypes found in North America. This is the largest case-control study to date associating GBV-C viremia and NHL risk. As GBV-C is known to be transmitted through blood products this may have important implications for blood safety.

Infection with cytomegalovirus (CMV) induces surface expression of major histocompatibility complex (MHC)-class-I-chain-related A (MICA), a ligand for NKG2D. This leads to improved recognition and elimination of infected cells by natural killer (NK) as well as CD8+ T cells. The MICA5.1 allele codes for a truncated protein. This study was performed to test whether impaired expression of a functional MICA protein would influence the susceptibility to severe CMV reactivation in immunocompromised individuals. In this study, the frequency of MICA5.1 was assessed by polymerase chain reaction in 230 Caucasian human immunodeficiency virus (HIV)-1-infected patients and in 219 healthy controls. Patients co-infected with hepatitis C virus (HCV) and GB virus-C served as controls. MICA5.1 allele was analyzed by polymerase chain reaction. Association of MICA5.1 homozygosity and risk of CMV reactivation was calculated by Pearson chi2 test. Comparison of patients with and without a history of CMV disease manifestation revealed that homozygous MICA5.1 genotype was present in a significantly higher frequency in patients with CMV reactivation (33%) than in those without (16%; p 0.032; odds ratio 0.330). The percentage was similar in HIV-1-infected patients and healthy controls. Furthermore, there was no difference in the frequency of MICA5.1 with respect to infection with HCV and GB virus-C. Our study provides the first in vivo demonstration of an association between homozygous MICA5.1 genotype and susceptibility to CMV reactivation in immunocompromised individuals.

Acute and chronic liver diseases are an assortment of disorders brought to the clinician's attention by abnormal liver function tests or specific signs and symptoms. The differential diagnosis includes disorders that have primary or secondary liver involvement. This paper will be limited to the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of the different viral liver diseases: A, B, C, D, E and G.

Unlabelled: HIV-infected individuals are frequently co-infected with different hepatitis viruses. HCV has been associated with impaired quality of life in non-HIV infected patients. Little is known concerning the quality of life in HIV-infected individuals in relation to the different viral co-infections. -, Patients and Methods: We investigated 250 patients who have answered HIV-SELT and EuroQoL (EQ-5D) questionnaires assessing quality of life. Data on HBsAg, anti-HBc, anti-HCV, and GBV-C-RNA were available for 191, 188, 189, 98 patients, respectively. HCV-RNA was tested in 33 of 35 anti-HCV positive patients. -, Results: There was no difference in quality of life in relation to active or past HBV-infection defined by HBsAg (n = 15) and anti-HBc in the absence of HBsAg (n = 84), respectively, for both overall HIV-SELT (p = 0.66, and p = 0.43, respectively) and visual EQ-5D (p = 0.93 and p = 0.64, respectively). However, anti-HCV positivity (n = 35) was associated with significantly impaired quality of life (HIV-SELT overall p<0.001). Importantly, no difference was found in relation to HCV-viraemia in anti-HCV positive patients (p = 0.77). In multivariate analysis anti-HCV positivity, employment status, HIV viral load and GBV-C were relevant to quality of life, with GBV-C being beneficial and HCV being negative. -, Conclusions: While HBV seems to play no role concerning quality of live in HIV-infected patients, the flavi-viruses HCV and GBV-C display opposing influence on quality of life. As quality of life was similarly impaired in HCV-viraemic and HCV-non-viraemic anti-HCV positive patients but better in GBV-C viraemic patients, this should be taken into account in the indication case of planned interferon therapy.

Background: Chronic fatigue syndrome (CFS) is an illness in search of an infectious etiology. GB virus-C (GBV-C) virus is a flavivirus with cell tropism and host defense induction qualities compatible with a role in producing the syndrome. The GBV-C genome is detectable in 4% of the population and 12% of the population is seropositive. The present study evaluated the association between infection with GBV and CFS., Methods: We used a commercial EIA to detect antibodies against the GBV-C E2 protein and a quantitative real-time RT-PCR assay to detect active GBV-C infection. Sera were from a case control study of CFS in Atlanta, Georgia. The Fisher's exact two-tailed test was used for statistical analysis., Results: Two of 12 CFS patients and one of 21 controls were seropositive for prior GBV-C infection and one control had viral RNA detected, indicating active infection. The results are not statistically different., Conclusion: We found no evidence that active or past infection with GBV is associated with CFS.

GB virus type C (GBV-C) causes persistent infection in humans, although the mechanism by which the virus avoids clearance by the host is unknown. To determine if amino acid polymorphisms in the GB virus type C (GBV-C) NS5A and E2 proteins alter response to interferon (IFN) therapy, we studied the sequence of GBVC NS5A and E2 obtained from people receiving IFN therapy. In addition, we expressed recombinant GBVC NS5A protein to determine if it interferes with RNA-activated protein kinase (PKR) function in vitro. GBVC NS5A amplified from a person whose virus was cleared by IFN therapy (IFN sensitive) demonstrated unique amino acid changes occurring in the region that aligns with the hepatitis C virus (HCV) IFN sensitivity-determining region (ISDR) compared with NS5A sequences from individuals who did not clear GBV-C (IFN resistant). There were no differences in the E2 sequences obtained from IFN-sensitive and IFN-resistant isolates. Using a yeast genetic system, IFN-resistant NS5A inhibited PKR-mediated phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) in yeast, whereas IFN-sensitive NS5A did not inhibit PKR function. GBV-C NS5A amino acid polymorphisms appear to be involved in response to IFN therapy, and IFN-resistant GBV-C NS5A inhibited PKR-mediated eIF2alpha phosphorylation in a yeast genetic system, suggesting a mechanism by which GBV-C may evade clearance by naturally occurring host antiviral responses.

Lymphoma is a common hematological malignancy. Hepatitis viruses, especially hepatitis B and hepatitis C, are known risk factors for development of non-Hodgkin lymphomas. However, there are a number of patients with hepatitis in whom no virus can be identified and it was therefore postulated that there may be other agents which may be causing hepatitis. Many new hepatitis viruses have indeed been identified and proposed to have possible roles in pathogenesis of many disorders. Hepatitis G virus (HGV) is an example of a newly detected hepatitis virus. Whethere there is a correlation between infection and development of non-Hodgkin's lymphoma is of interest. Therefore an appraisal of the prevalence of HGV RNA among patients with B cell non-Hodgkin's lymphoma comparing with healthy control subjects was performed. According to the literature review, three reports covering 247 cases of non Hodgkin's lymphoma were recruited. The overall prevalence of HGV RNA positivity was found to be 7.2 % (18/247). Of the three reports, only two had complete data on the prevalence in both patients with B cell non-Hodgkin's lymphoma and healthy control subjects andwere used for further metanalysis study, covering 178 cases and 355 healthy subjects. The overall antibody positive rate in the patients and healthy subjects were 8.4 % (15/178) and 0.8 % (3/355), respectively, with an odds ratio is 10.8. According to this study, it can be seen that individuals who are HGV RNA positive may be at very high risk of B cell non-Hodgkin's lymphoma development.

Aim: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum., Methods: Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological, histological assays., Results: Serum HGV RNA was detectable in all the 3 Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohis-tochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes. RT-PCR and quantitative PCR results showed that HGV could replicate in liver., Conclusion: The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.

GB virus C (GBV-C) is a nonpathogenic member of the Flaviviridae family most closely related to hepatitis C virus (HCV). Infection is common in healthy and immunocompromised people and may persist for years. GBV-C infection is associated with improved survival, improved AIDS-free survival, higher CD4(+) T-cell counts, and lower HIV viral loads in HIV-infected people compared with people infected with HIV but not GBV-C. The mechanism of this effect is not yet clear, but GBV-C has been shown to inhibit HIV replication in vitro through increased synthesis and secretion of anti-HIV b-chemokines MIP-1a, MIP-1b, RANTES, SDF-1, and SDF-2 and downregulation of CCR5 receptor expression. GBV-C also inhibits apoptosis of its host cell, similar to HCV. GBV-C E2 protein in serum has also been associated with prolonged survival in HIV infection; recent evidence indicates that GBV-C E2 protein may neutralize HIV infection in vitro.

The paper reviews the available information on the newly discovered viruses originally supposed to cause post-transfusion hepatitis. GBV-C/Hepatitis G virus belongs to the Flaviviridae family, and can be transmitted parenterally like Hepatitis C virus. Its role in causing hepatitis or other diseases has not been proved yet. The other newly discovered viruses contain single-stranded circular DNA, with a wide range of sequence divergence. These viruses can be transmitted not only with blood and blood products but via fecal-oral route as well. They are unique among enterally transmitted viruses in the sense that the virus persists for years in the human body, therefore their genomes may be detected in the blood of the healthy population in high percentage. One of the genotypes of TTV is suspected to cause hepatitis. High TT virus load was found as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease. It is not clear yet, whether TTV-like minivirus and SEN virus cause any illnesses.

Aim: To determine the pathogenicity of GB virus C (GBV-C) on liver and the effects of its co-infection on the clinical features and prognosis of patients with hepatitis B and C., Methods: Cross-sectional study was carried out in 413 patients with acute, chronic hepatitis B or liver cirrhosis, and in 67 hemodialysis patients. A 20-month prospective cohort study was carried out in 95 hepatitis B and 80 hepatitis C patients. A reverse transcriptase nested polymerase chain reaction (RT-nPCR) of the 5'-noncoding region was used to detect circulating GBV-C RNA. Liver function was determined by an automated analyzer for all patients., Results: The prevalence of GBV-C in the high-risk populations with the virus transmitted via blood was high, ranging from 16.2 to 28.8 %. Co-infection with GBV-C in hepatitis B patients did not affect the clinical features of the disease or liver function. The dialysis patients infected with GBV-C alone did not develop functional changes to the liver. Prospective cohort study showed that GBV-C co-infection did not affect the clinical features, prognosis or negative serum conversion rate of chronic hepatitis B and C., Conclusion: The results suggest that GBV-C has no marked pathogenicity on liver, so it may not be a hepatitis virus.

Background: The etiology of B-cell lymphoproliferative disorders (LPDs) of the skin has still to be elucidated. So far, Borrelia sp. has been identified as the causative agent of some cases of B-cell LPDs of the skin. Apart from bacterial pathogens, recent studies suggested that also flaviviruses, in particular hepatitis C (HCV) and G (HGV) viruses, may be involved in the pathogenesis of B-cell non-Hodgkin's lymphomas (NHLs). Most studies were performed in patients with known HCV infection, but the overall frequency of HCV- and HGV-RNA in tumoral tissue of primary cutaneous B-cell lymphomas (CBCLs) is unknown., Methods: We examined 23 tumor biopsies of various forms of CBCLs by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing for the presence of HCV and HGV., Results: HCV-RNA sequences were detected in seven of 23 (30%) of the tumor biopsies. In contrast, RNA sequences of HGV were not detected in any of the tumors., Conclusions: Interestingly, the presence of HCV in our series of primary CBCLs was not restricted to a distinct clinicopathologic subform. HCV which can infect B cells, may play a role in pathogenesis of one-third of CBCLs, whereas HGV is not involved in CBCLs. Further molecular studies and therapeutic trials are needed to clarify the putative pathogenetic role of HCV in CBCLs.

Objective: To observe the relationship between the amount of HBV DNA in serum/liver tissue and HGV infection in patients with chronic hepatitis B (CH-B) for exploring the effect of HGV infection on hepatitis B virus (HBV) replication of CH-B., Methods: HGV RNA in serum, HGV nonstructural region 5 (NS5) antigen (HGV Ag) in liver tissue and the amount of HBV DNA in serum, liver tissue were detected for 56 patients with CH-B by reverse transcription-polymerase chain reaction (RT-PCR) assay, peroxidase antiperoxidase (PAP) immunohistochemical method and fluorescence quantitative PCR assay, respectively. Then the relationship between HGV Ag expression in liver tissue and HGV RNA expression in serum was analysed and the amount of HBV DNA in serum and liver tissues from the serum HGV RNA or liver tissue HGV Ag positive patients were compared with those of the serum HGV-RNA or liver tissue HGV Ag negative patients, respectively., Results: Ten (17.9%) and eight (14.3%) patients were positive for serum and liver tissues,respectively.HGV RNA expression in serum was closely related to HGV Ag expression in liver tissues, but there was HGV RNA in serum from some of the liver tissues HGV Ag negative patients ?cases of HGV RNA and HGV Ag positive or negative,HGV RNA positive but HGV Ag negative, HGV RNA negative but HGV Ag positive, respectively: 5,43,5,3,(P<0.01). There was no significant difference in the amount of HBV DNA in serum and liver tissues between HGV RNA or HGV Ag positive and negative patients (P>0.05)., Conclusions: HGV infection may not affect HBV replication. Liver is the site of HGV replication, but HGV probably also replicates in extrahepatic tissues. HGV hepatic pathogenicity is probably mild and further studies are still needed.

Objective: To study the pathogenic effect of hepatitis G virus (HGV) infection on hepatic failure., Methods: Using the RT-PCR and EIA techniques to detect HGV RNA and anti-HGV in sera of hepatic failure patients and compare them with their liver function and mortality rates., Results: There was no significant difference about the positive rates of HGV among acute hepatic failure, subacute hepatic failure and chronic hepatic failure groups (X(2)=2.54, P>0.05). The level of ALT in HGV-positive group was slightly lower than that in HGV-negative group. The concentration of bilirubin and globulin was higher in HGV-positive group than HGV-negative group, and the concentration of albumin in HGV-positive group was significantly lower than that in HGV-negative group (t=2.59, P<0.05). The mortality rate in HGV-positive group was significantly lower than that in HGV-negative group (X(2)=4.68, 0.01

Hepatitis C virus (HCV) and hepatitis G virus (HGV) belong to the same family of flaviviridea. A causative role of HCV infection in the pathogenesis of non-Hodgkin's lymphoma (NHL) has been discussed widely. Little is known about the possible association between NHL and HGV discovered recently. In this study, anti-HCV and HGV-RNA prevalence were investigated in a group of 70 patients with NHL. The results were compared to a control group of 70 age- and sex-matched healthy subjects. One patient in each group (1.4%) was found to be anti-HCV-positive; the difference was not statistically significant (P > 0.05). Five subjects in the patient group (7.1%) were positive for HGV-RNA, while a single subject was positive in the control group (1.4%); the difference was not statistically significant (P > 0.05). Odds ratios for anti-HCV and HGV-RNA were 1 and 5.30, respectively. Our findings suggest that neither HCV nor HGV are causative or contributing factors in the aetiopathogenesis of NHL.

After the discovery of hepatitis A, B, C, D and E viruses, several lines of evidence suggested that an additional hepatitis agent (s) might exist. Molecular approaches led sequentially to the discoveries of GBV-C/HGV, TTV and more recently SENV. At issue is whether these agents cause non - A non - E hepatitis and/or some extrahepatic diseases. These problems are discussed in present paper, considering the newest data from literature.

GB virus-B (GBV-B) is a member of the Flaviviridae family of viruses. This RNA virus causes acute resolving hepatitis in experimentally infected tamarins, but its natural host remains unknown. GBV-B and a related virus, GBV-A, were recovered from serum containing the "GB agent," which was believed to have originated from a surgeon (initials: GB) with acute hepatitis. GBV-B has special interest because it is the virus related most closely to hepatitis C virus, which is an important cause of acute and chronic liver disease in humans. In the present study, we found that the host range of GBV-B includes owl monkeys. Tamarins and owl monkeys belong to two different families of New World monkeys. The natural history of GBV-B in the two owl monkeys studied was similar to that previously found for tamarins and was characterized by early appearance of viremia and viral clearance. However, the peak viral titers of GBV-B observed in owl monkeys (10(5) genome equivalents [GE] /ml) were lower than those observed in experimentally infected tamarins (10(7)-10(8) GE/ml) and acute hepatitis was observed in only one animal. If GBV-B were indeed a virus of humans, it would be expected to infect chimpanzees, a surrogate of humans, because all recognized human hepatitis viruses are transmissible to chimpanzees and cause hepatitis. However, in the present study, we failed to transmit GBV-B to a naive chimpanzee. In addition, a second naive chimpanzee transfected intrahepatically with RNA transcripts from an infectious clone of GBV-B did not become infected. Thus, chimpanzees are apparently not susceptible to GBV-B. Finally, we failed to detect GBV-B in acute-phase serum from surgeon GB. Our data suggest that GBV-B is not a human virus and that GBV-B, like GBV-A, is a virus of New World monkeys., (Copyright 2001 Wiley-Liss, Inc.)

Objective: To observe the long-term effect of hepatitis G virus (HGV) coinfection on hepatic pathological changes of patients with chronic hepatitis B (CHB) and explore the pathogenicity of HGV., Methods: Menghini method liver biopsy was performed on 45 patients with CHB twice with an interval of 5 years on a voluntary basis. The liver tissue of 21 cases was HGV nonstructural region 5 (HGV NS5) antigen positive by peroxidase anti-peroxidase (PAP) immunohistochemical staining assay (HGV coinfection group) in these two tests, and 24 cases were negative (HGV noncoinfection group). There was no significant difference in age, sex, course of disease, amount of serum HBV-DNA by competitive quantitative polymerase chain reaction assay and severity of hepatic pathological leisions between these two groups (P < 0.05) and they were treated with the same scheme and without sustained curative effeect. The hepatic pathological changes of the two groups after 5 years were compared and analysed retrospectively., Results: There was no significant difference in basic hepatic pathological change, severity of inflammatory activity grade and fibrosis stage in these two groups. The numbers of cases of inflammatory activity grade G1, G2, G3, and G4 were 3, 7, 7, and 4 in HGV coinfection group, and 5, 8, 7, and 4 in HGV noncoinfection group in the beginning of observation; and were 3, 5, 7, and 6 in HGV coinfection group, and 4, 6, 8, and 6 in HGV noncoinfection group after 5 years. The numbers of cases in fibrosis stages S1, S2, S3, and S4 were 4, 7, 7, and 3 in HGV coinfection group, and 6, 8, 6, and 4 HGV noncoinfection group in the beginning of observation; and were 3, 6, 5, 7 in HGV coinfection group, and 4, 7, 5, and 8 in HGV noncoinfection group after 5 years (P > 0.05)., Conclusion: HGV coinfection does not lead to the activation of hepatic pathological changes and does not speed up the progression of fibrosis in patients with CHB. HGV coinfection does not play an obvious role in long-term hepatic pathological changes of patients with CHB. HGV has at most a mild hepatic pathogenicity.

Three groups of patients have been studied longitudinally for 24 months to analyze the role of hepatitis G virus (HGV) in hepatic disease. Group 1 consisted of 50 patients with non-B, non-C chronic hepatitis, group 2 consisted of 44 hemodialyzed patients, and group 3 consisted of 50 healthy blood donors. The presence of HGV RNA was detected by both reverse transcription-polymerase chain reaction (RT-PCR) and capillary zone electrophoresis (CZE). At the baseline visit the HGV RNA was detected in seven out of 50 patients with non-B, non-C chronic hepatitis, in two out of 44 hemodialyzed patients, and in three out of 50 healthy blood donors. HGV-infected hemodialyzed patients and HGV viremic blood donors had serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within normal limits. During the follow-up period the two HGV-positive hemodialyzed patients and the three infected healthy blood donors did not show any sign of hepatic disease. There were no significant differences between HGV-positive patients in the three groups at the beginning and at the end of the follow-up. No considerable deterioration of general health conditions was observed on the basis of clinical and laboratory data in HGV-positive chronic hepatitis patients. Finally, HGV does not seem to be responsible for hepatic disease.

Aim: To study the pathogenicity of hepatitis G virus (HGV) and observe the genesis and pathological process of hepatitis G., Methods: HGV-RNA in serum was detected by RT-PCR assay. The immunohistochemical assays of liver tissue were performed with HGV monocoloned antibody (McAb) expressed from the region of HGV NS5 nucleic acid sequence. The clinical and pathological data of 52 patients with hepatitis G were discussed. In animal experiment, the Chinese Rhesus monkeys were infected with the serum of a patient with HGV infection. And the dynamic changes in serology and liver histology of animals were observed., Results: One hundred and fifty-four patients with HGV-RNA positive were selected from 1552 patients with various kinds of hepatitis. Of 154 patients with HGV infection, 52 were infected with HGV only, which accounted for 33.8 (52/154) and 102 with positive HGV-RNA were super-infected with other hepatitis viruses, which accounted for 66.2 (102/154). The clinical and pathological observation showed that the acute and chronic hepatitis could be induced by HGV. The slight abnormality of transaminases ALT and AST in serum of monkeys lasted nearly 12 months and histological results showed a series of pathological changes., Conclusion: HGV is a hepatotropic virus and has pathogenicty.

Background: Prevalence and pathogenicity of hepatitis G virus infection in long-term renal transplant recipients, are not fully known., Aim: To evaluate long-term impact of HGV infection on liver disease of renal transplanted patients., Patients and Methods: A total of 155 hepatitis B surface antigen negative kidney transplant recipients, followed for a mean of 11 years after renal transplantation, were studied. Of these 48 (31%) patients had persistently elevated serum aminotransferase values. Frozen serum samples were tested for HGV-RNA and HCV-RNA by nested reverse transcribed polymerase chain reaction, and for anti-hepatitis G virus and anti-hepatitis C virus by enzyme-linked immunosorbent assay Hepatitis C virus-RNA was typed by a line probe assay and quantified by a branched DNA signal amplification assay, Results: Hepatitis G virus-RNA was detected in 37 (24%) patients and anti-hepatitis G virus in another 26 (17%). Seventy (45%) patients had serum anti-hepatitis C virus and 63 of these (90%) had serum hepatitis C virus-RNA. Hepatitis G virus-RNA positive and negative patients were similar in terms of age, sex, duration of dialysis, rate of transfusion, chronic liver disease, rate of hepatitis C virus infection and immunosuppressive therapy. Fifteen (41%) hepatitis G virus-RNA seropositive patients were hepatitis C virus co-infected. Hepatitis C virus-RNA levels were significantly lower in the 15 hepatitis C virus/hepatitis G virus co-infected patients than in the 48 patients with hepatitis C virus infection only (2.2 vs 10.8 MEq/ml, p = 0.02). Only 3 hepatitis G virus carriers had persistently elevated alanine aminotransferase compared to 29 hepatitis C virus carriers (14% vs 60%, p < 0.001), 10 patients co-infected with both hepatitis G virus and hepatitis C virus, and in 6 patients with neither infection (67% vs 8%, p < 0.001)., Conclusions: Hepatitis G virus infection is common among kidney transplant patients, it carries a low risk of chronic liver disease even in long-term follow-up. Low levels of hepatitis C virus-RNA found in hepatitis G virus carriers suggest an interaction between these two viruses in immunosuppressed patients.

This lecture includes three sections. Firstly, the concepts of genotype, subtype and quasi-specie are described. The appearance of virus is correlated with the evolution of the medical picture, and their resistance to antiviral agents. Secondly, the most modern genetical and molecular biology techniques, including DNA sequencing are studied. Thirdly, some examples of the investigation lines carried out at the Microbiology Department of the Granada Medicine School are explained, especially regarding to papillomavirus, hepatitis C virus, hepatitis G virus, virus associated to transfusions (TTV) and human immunodeficiency. The great transcendence that the genetical variability has to establish pathogeny and therapy control is emphasized.

Objective: To study the clinical, enzymatic and liver pathological changes in patients with hepatitis G virus (HGV) infection., Methods: RT- nested PCR was applied to detect HGV RNA in 368 patients with hepatic diseases. The liver biopsy tissue from one liver cirrhosis patient with simple HGV infection was examined., Results: Simple HGV RNA positive were found in 7 cases of 71 acute hepatitis jaundice, in 22 cases of 155 chronic hepatitis and in 3 cases of 51 liver cirrhosis. The immunohistochemistry of the liver biopsy tissue from a liver cirrhosis patient showed HGV NS5 antigen positive. However, HGV infection might occur simply or in combination with hepatitis B or C virus or super infected., Conclusions: HGV RNA could be detected in acute hepatitis jaundice, chronic hepatitis, hepatitis B or C carriers, liver cirrhosis and hepatocellular carcinoma. HGV is proved to be a hepatotropic virus by pathological examination and immunohistochemistry, the virus located in the cytoplasm of the liver cells. It may cause chronic hepatitis and even liver cirrhosis, so HGV is pathogenic to liver tissue.