Replication of hepatitis C virus in peripheral blood mononuclear cells

Qian, Cheng; Camps, J.; Maluenda, Maria D.; Civeira, M.P.; Prieto, Jesús

doi:10.1016/s0168-8278(05)80674-9

Cited by 88 publications

(48 citation statements)

References 8 publications

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“…25 In this article we show that the transcriptional expression of Mn-SOD is increased in PBMC from patients with chronic hepatitis C. In this disease, both PBMC and the liver have been shown to be infected by HCV. 1,26 The increase in Mn-SOD here reported appear to be related to active viral infection because Mn-SOD was found to significantly decrease in patients with sustained virological and biochemical response following IFN therapy. Because enhanced Mn-SOD expression appears to be an adaptive response to increased oxidative stress, 15,16 our observations support the concept that disturbed intracellular redox state may be implicated in the pathogenesis of HCV infection.…”

Section: Discussionmentioning

confidence: 75%

Superoxide Dismutase in Patients With Chronic Hepatitis C Virus Infection

Larrea

Beloqui

Muñoz-Navas

et al. 1998

Free Radical Biology and Medicine

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110

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Abstract-It has been reported that hepatitis C virus (HCV) may cause oxidative stress in infected cells. Patients with chronic hepatitis C exhibit an increased production of tumor necrosis factor-␣ (TNF␣), a cytokine that can produce oxidative stress by stimulating the generation of reactive oxygen species (ROS). Cell defense against ROS includes overexpression of Mn-superoxide dismutase (SOD), an inducible mitochondrial enzyme. To investigate cell defense against oxidative stress in HCV infection, we analyzed Mn-SOD mRNA in liver and in peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis C. Mn-SOD expression in PBMC was significantly increased in patients with HCV infection. Patients with sustained virological and biochemical response after therapy showed significantly lower Mn-SOD than patients with positive viremia. By contrast, Mn-SOD expression was not enhanced in the liver of patients with chronic hepatitis C. The values of Mn-SOD mRNA did not correlate with TNF␣ mRNA expression, viral load, or liver disease activity. Our results indicate that in HCV infection an induction of Mn-SOD was present in PBMC but absent in the liver, suggesting that this organ could be less protected against oxidative damage. Oxidative stress could participate in the pathogenesis of HCV infection.

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Section: Discussionmentioning

confidence: 75%

Superoxide Dismutase in Patients With Chronic Hepatitis C Virus Infection

Larrea

Beloqui

Muñoz-Navas

et al. 1998

Free Radical Biology and Medicine

Self Cite

110

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“…Indeed, negativestrand RNA has been reported in mononuclear cells such as B and T lymphocytes and monocytes, [11][12][13][14][15] in polynuclear lymphocytes, 16,17 and even in hematopoietic progenitor cells. 18 Moreover, the viral genomic RNA has been detected more frequently in PBMCs from nonresponders 19 to interferon (IFN) treatment. Interestingly, considering viral dynamics such as virus half-life, the suppressing effect on viral replication observed through treatment appears consistently slower in PBMCs than in serum.…”

Section: Introductionmentioning

confidence: 99%

Differential distribution and internal translation efficiency of hepatitis C virus quasispecies present in dendritic and liver cells

Laporte

Bain

Maurel

et al. 2003

Blood

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Hepatitis C virus (HCV) is predominantly a hepatotropic virus. Nonetheless, there is mounting evidence that hematopoietic cells may support HCV replication. The HCV 5 untranslated region (5UTR), responsible for initiation of viral translation, via an internal ribosome entry site (IRES), has been previously described to contain specific nucleotide substitutions when cultured in infected lymphoid cells. Our purpose was to establish whether the 5UTR polymorphism of quasispecies from 3 cell compartments (liver, peripheral blood mononuclear cells [PBMG], and monocyte-derived dendritic cells IntroductionHepatitis C virus (HCV) is a positive strand RNA virus that establishes a chronic infection in more than 80% of cases. Chronicity frequently leads to liver cirrhosis and hepatocellular carcinoma, 1 making HCV infection the first indication for liver transplantation. Poor fidelity of the viral RNA-dependent RNA polymerase results in the coexistence of closely related but distinct variants called quasispecies, which are likely involved in viral persistence. 2,3 There is mounting evidence for an extrahepatic replication based on the frequent association of hepatitis C infection with lymphoproliferative disorders such as cryoglobulinemia and nonHodgkin lymphomas (reviewed by Dammacco et al 4 ), and the possibility of experimental transmission of non-A non-B hepatitis to a chimpanzee by mononuclear leucocytes from a chronically infected patient. 5 Supporting the results of Hellings et al, 6 severe combined immunodeficiency (SCID) mice have been shown to be susceptible to persistent HCV infection after injection of human HCV-positive peripheral blood mononuclear cells (PBMCs). In addition, tissue compartmentalization of the HCV genome has been described during HCV infection 7,8 and coinfection with HIV. 8 Finally, the detection of HCV RNA-negative strand as the theoretical intermediate of replication, although somewhat controversial, 9,10 has been well documented in PBMCs. Indeed, negativestrand RNA has been reported in mononuclear cells such as B and T lymphocytes and monocytes, [11][12][13][14][15] in polynuclear lymphocytes, 16,17 and even in hematopoietic progenitor cells. 18 Moreover, the viral genomic RNA has been detected more frequently in PBMCs from nonresponders 19 to interferon (IFN) treatment. Interestingly, considering viral dynamics such as virus half-life, the suppressing effect on viral replication observed through treatment appears consistently slower in PBMCs than in serum. 20 On the basis of these studies, one can argue that a specific replicative dynamics of HCV exists in PBMCs.The relationship between quasispecies and replication in PBMCs is unclear. In a previous study we demonstrated, in the serum of a patient chronically infected with HCV, 21 the coexistence of internal ribosome entry site (IRES) quasispecies segregating according to their respective translation efficiencies in lymphoid and nonlymphoid optimal IRES. The HCV IRES responsible for the capindependent initiation of viral RNA translation 2...

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“…It is suspected that TRX protein in the liver may be produced by the hepatocytes and induced by inflammatory cells located among or around the hepatocytes. In view of the fact that TRX is produced by lymphocytes infected by viruses, such as HTLV-1 and Epstein-Barr viruses (23,24), and that HCV can infect lymphocytes and replicate inside them (25,26), it has been suggested that serum TRX may originate in HCVinfected peripheral blood mononuclear cells. That may be the reason why there was no correlation between the serum TRX level and the TRX level in the liver.…”

Section: Discussionmentioning

confidence: 99%

Expression of thioredoxin and thioredoxin-binding protein-2 in the liver of patients with chronic hepatitis C as a predictor of response to interferon therapy

Hamano

Seo²,

Kato³

et al. 2006

Int J Mol Med

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Abstract.Oxidative stress contributes to the pathogenesis of various hepatic injuries. Thioredoxin (TRX) is an indicator of oxidative stress, reported to be increased in the serum of patients with chronic hepatitis C with the progression of fibrosis. The aim of this study was to evaluate the clinical significance of the expression of TRX and thioredoxin-binding protein-2 (TBP-2), which is a negative regulator of TRX function, in the liver of patients with chronic hepatitis C and the relationship of this to the efficacy of interferon (IFN) treatment. A retrospective study was performed using the liver biopsy specimens obtained before IFN treatment from 69 patients with chronic serotype 1 hepatitis C virus (HCV) infection. TRX and TBP-2 mRNA levels in the liver biopsy specimens were amplified by real-time RT-PCR. The serum TRX protein level was estimated with a sandwich enzyme-linked immunosorbent assay kit, and the expression of TRX protein in the liver was examined immunohistochemically in 19 patients. There was no association between the serum TRX level and the TRX level in the liver. There was a significant correlation between the expression level of TRX protein in the liver and the TRX mRNA level in the liver. TRX and TBP-2 levels in the liver tended to decrease slightly with increased fibrosis stage, although not significantly. The TRX level in the liver tended to increase with hepatitis activity index, although not significantly. TBP-2 mRNA levels in the liver were significantly higher in responders than non-responders to the IFN therapy (p<0.05). Among patients who had a high viral load of >850 KIU/ml, the TRX level in the livers of non-responders was significantly lower than that in the livers of responders (p<0.05). TRX and TBP-2 mRNA levels in the liver before IFN therapy may predict the outcome of IFN therapy in patients with chronic serotype 1 HCV infection.

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Replication of hepatitis C virus in peripheral blood mononuclear cells

Cited by 88 publications

References 8 publications

Superoxide Dismutase in Patients With Chronic Hepatitis C Virus Infection

Superoxide Dismutase in Patients With Chronic Hepatitis C Virus Infection

Differential distribution and internal translation efficiency of hepatitis C virus quasispecies present in dendritic and liver cells

Expression of thioredoxin and thioredoxin-binding protein-2 in the liver of patients with chronic hepatitis C as a predictor of response to interferon therapy

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