HCV replication in PBMC and its influence on interferon therapy

Gong, Guozhong; Lai, Li-Ying; Jiang, Yong-Fang; He, Yan; Su, Xian-shi

doi:10.3748/wjg.v9.i2.291

Cited by 52 publications

(41 citation statements)

References 34 publications

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“…Interestingly, patients with detectable negative-strand HCV RNA in PBMCs had lower interferon (IFN) sustained response rates compared to those without detectable negative-strand HCV RNA in PBMCs. 103 Thus, it is provocative to speculate that low-level replication of HCV in PBMCs may lead to reactivation of HCV after termination of therapy and/or predict response to therapy. 80,99,100,[102][103][104][105] As reviewed elsewhere, HCV is likely involved in several neurologic syndromes.…”

Section: Clinical Implications Of Extrahepatic Replicationmentioning

confidence: 99%

“…103 Thus, it is provocative to speculate that low-level replication of HCV in PBMCs may lead to reactivation of HCV after termination of therapy and/or predict response to therapy. 80,99,100,[102][103][104][105] As reviewed elsewhere, HCV is likely involved in several neurologic syndromes. 16 While central nervous system (CNS) involvement is less frequent, the detection of negative-strand HCV RNA in the CNS 29 suggests a potential link between HCV and these extrahepatic pathol- ogies.…”

Section: Clinical Implications Of Extrahepatic Replicationmentioning

confidence: 99%

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Extrahepatic replication of HCV: Insights into clinical manifestations and biological consequences

2006

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Section: Clinical Implications Of Extrahepatic Replicationmentioning

confidence: 99%

Section: Clinical Implications Of Extrahepatic Replicationmentioning

confidence: 99%

Extrahepatic replication of HCV: Insights into clinical manifestations and biological consequences

2006

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“…These include mixed cryoglobulinemia, non-Hodgkin's lymphoma, cutaneous vasculitis, membranoproliferative glomerulonephritis, neuropathy, lymphoproliferative disorders, porphyria cutanea tarda, lichen planus, and Sjogren's syndrome (1, 7). HCV is reported to replicate in extrahepatic sites like interstitial cells of the kidney, acinar cells of the pancreas, peripheral blood mononuclear cells, and mononuclear cells of lymph nodes (5,14). Currently, the diagnosis of HCV infection is achieved by the detection of HCV RNA in plasma or serum.…”

mentioning

confidence: 99%

Whole Blood as an Alternative to Plasma for Detection of Hepatitis C Virus RNA

Daniel¹,

David²,

Grant³

et al. 2008

J Clin Microbiol

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Peripheral blood mononuclear cells are reported to be one of the extrahepatic replication sites contributing to the persistence of hepatitis C virus (HCV) infection. Whole-blood and plasma samples from 61 individuals were compared as sources for the detection of HCV RNA. Forty-four of the individuals were receiving antiviral therapy, while 17 were treatment naïve. The quantitation of HCV RNA was done by a sensitive in-house real-time reverse transcription-PCR. When the viral loads in the two types of samples were compared, a correlation coefficient of 0.858 (P < 0.001) was found, indicating that plasma and whole blood are equally acceptable sources for testing for HCV RNA.Approximately 18 million people in India are estimated to be infected with hepatitis C virus (HCV) (13). HCV infection is chronic in 75% to 85% of infected individuals (3). Chronic HCV infection can lead to hepatocellular carcinoma after many years. Even though hepatocytes are the major replication site for HCV, a broad range of extrahepatic complications and diseases are associated with chronic HCV infection. These include mixed cryoglobulinemia, non-Hodgkin's lymphoma, cutaneous vasculitis, membranoproliferative glomerulonephritis, neuropathy, lymphoproliferative disorders, porphyria cutanea tarda, lichen planus, and Sjogren's syndrome (1, 7). HCV is reported to replicate in extrahepatic sites like interstitial cells of the kidney, acinar cells of the pancreas, peripheral blood mononuclear cells, and mononuclear cells of lymph nodes (5,14). Currently, the diagnosis of HCV infection is achieved by the detection of HCV RNA in plasma or serum. Testing for HCV RNA in plasma or serum might give a false-negative result if HCV RNA is present inside peripheral blood mononuclear cells (PBMCs) or as precipitates of immune complexes and cryoglobulin aggregates. Hence, the recovery of RNA from whole blood is likely to help with the diagnosis of HCV infection in individuals with low HCV loads, since both intracellular RNA and plasma RNA are detected. This can also have implications in the monitoring of individuals receiving antiviral therapy (12). Screening for HCV by the use of wholeblood samples will be useful, since all blood components are screened and the time required to separate plasma and serum is saved (leaving the remaining sample usable for serology). This study was done to investigate whether whole blood is more sensitive than plasma for the detection of HCV RNA and to assess the impact of testing of whole blood on the viral load result.Blood samples were collected from 61 patients who came to the Department of Clinical Virology, Christian Medical College, as referrals from the Departments of Hematology, Gastroenterology, and Nephrology. All patients were recruited after they provided verbal consent, in addition to a general consent that is obtained in our hospital for all investigations as part of our routine patient management. These 61 patients consisted of 44 men and 17 women with a mean age of 42 years (age range, 16 to 66 years). Of thes...

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“…HCV genotype and the baseline level of viremia have been pointed out as the most important predictive factors of responsiveness to IFN therapy [22] . However, several studies suggested that other factors, such as the heterogeneity of virus population [23] and replication in PBMC [24] , might also influence the effectiveness of therapy. Like most RNA viruses, HCV circulates in the human host as a complex population of different but closely related viral variants, commonly referred to as quasispecies [25] .…”

Section: Discussionmentioning

confidence: 99%

Expression of hepatitis C virus hypervariable region 1 and its clinical significance

Zhang¹

2003

WJG

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AIM:To explore the properties of hypervariable region 1 (HVR1) in the envelope 2 gene of hepatitis C virus by analyzing the reactivity of HVR1 fusion proteins from different Chinese HCV strains with sera of patients with chronic hepatitis C and by comparing their reactivity between interferon therapy responders and non-responders. METHODS:Gene fragments of HVR1 of four HCV strains (three genotype 1b and one genotype 2a) were amplified from pGEMT-E2 plasmids and sub-cloned into pQE40 vectors respectively to construct recombinant expression plasmids which expressed HVR1 fused downstream to DHFR in Escherichia coli strain TG1. The purified DHFR-HVR1 proteins were then used to detect the anti-HVR1 antibodies in 70 serum samples of patients with chronic hepatitis C. RESULTS:Four DHFR-HVR1 fusion proteins were successfully expressed in E.coli (320-800 ug fusion proteins per 100 ml culture). Each fusion protein (SH1b, BJ1b, SD1b and SD2a) reacted with 72.8 % (51/70), 60 % (42/ 70), 48.6 % (34/70), and 58.6 % (41/70) of the anti-HCV positive patients' sera respectively by ELISA. 57.1 % (4/ 7) of non responders reacted with all four HVR1 fusion proteins, while only 15.3 % (2/13) of responders reacted with all of them. The O.D. values of sera from IFN therapy responders were significantly higher than those of non responders (P<0.05). CONCLUSION:The selected HVR1 fusion proteins expressed in E. coli can broadly react with HCV-infected patients' sera. The intensity and/or quality of the immune response against HCV may be a critical factor determining the response to interferon treatment. With the evolution of virus strains, anti-HVR1 antibodies can not neutralize all the quasispecies. A polyvalent and high immunogenic vaccine comprising a mixture of several HVR1 sequences that cover the reactivity of most HCV isolates may be useful. INTRODUCTIONHepatitis C virus (HCV) is the major etiologic agent of blood transfusion-associated and sporadic non-A non-B hepatitis worldwide. About 70 % of the infections become chronic, among which a significant proportion eventually develops cirrhosis and hepatocellular carcinoma. Despite recent success after the combination therapy with Interferon-α and ribavirin [1][2][3] , about 60 % of patients still fail to respond. Thus, the development of HCV vaccine is especially important, but it remains an urgent challenge due to the high mutation rate of HCV.Multiple lines of evidence indicate that one of the principal neutralization determinants corresponds to the hypervariable region 1 (HVR1), which is located in the amino-terminus of E2 of HCV (nt1150-1230). Zibert et al [4] found that an early appearance of antibodies directed to HVR1 is associated with acute self-limiting infection of HCV, while the persistence of HVR1 antibodies is associated with chronic HCV infection. Antibodies against HVR1 have been shown to block adsorption to susceptible cells in vitro [5,6] . Animal antibodies raised against this region have provided effective prophylaxis in chimpanzee challenge experiments...

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HCV replication in PBMC and its influence on interferon therapy

Cited by 52 publications

References 34 publications

Extrahepatic replication of HCV: Insights into clinical manifestations and biological consequences

Extrahepatic replication of HCV: Insights into clinical manifestations and biological consequences

Whole Blood as an Alternative to Plasma for Detection of Hepatitis C Virus RNA

Expression of hepatitis C virus hypervariable region 1 and its clinical significance

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