Immunopathogenesis of Hepatitis C Virus Infection: Multifaceted Strategies Subverting Innate and Adaptive Immunity

Kanto, Tatsuya; Hayashi, Norio

doi:10.2169/internalmedicine.45.1530

Cited by 72 publications

(73 citation statements)

References 94 publications

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“…(ii) Secondly, aetiological factors of the liver disease. Both hepatitis C virus (HCV) and neo-antigens generated by the action of alcohol on the liver membranes have been reported as potent stimuli of the innate and acquired immunity [44,45]. No differences between these two factors were detected in patients analysed in our study.…”

Section: Cd25mentioning

confidence: 54%

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Márquez¹,

Fernández-Gutiérrez²,

Montesdeoca³

et al. 2009

Clinical and Experimental Immunology

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SummaryThe objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25 + , CD122 + ), effector function (CD8 + CD45RO + CD57 + ), apoptosis (CD95 + ) and regulatory abilities, either by analysis of the membrane expression of co-stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4 + CD25 high forkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation-induced death, even in non-advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen-induced immunopathology.

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Section: Cd25mentioning

confidence: 54%

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Márquez¹,

Fernández-Gutiérrez²,

Montesdeoca³

et al. 2009

Clinical and Experimental Immunology

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“…In the present study, no relationship between ALT and HCV RNA was found in the majority of acute cases, with the exception of two chronic patients who showed a positive correlation between viral load and liver enzymes during the follow-up. It remains possible that both viral and host immune factors might contribute to the polymorphic features as well as the outcome of HCV infection (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Viral clearance or persistence after acute hepatitis C infection: Interim results from a prospective study

et al. 2008

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“…The CD8+ T cells can eliminate HCV from the liver through two mechanisms: inducement of apoptosis in infected hepatocytes; and suppression of replication by the production of IFN-γ [22,65]. The CTL response is less vigorous in chronically infected patients than in those presenting acute infection [4].…”

Section: Cell Response To Hcvmentioning

confidence: 99%

Pathogenesis of hepatitis C: HCV consensus 2007

Viso¹

2007

Braz J Infect Dis

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The chronic hepatitis C virus (HCV) infects approximately 130 million people worldwide [1]. It is estimated that approximately 15% of HCV-infected individuals eliminate the virus spontaneously, that 25% develop a mild form of the disease, and that 60% develop the chronic progressive form [2]. The elimination or persistence of HCV infection depends on the balance between the effectiveness, specificity and rapidity of the innate and adaptive immune responses, as well as on the HCV replication rate [3]. Persistence of HCV can also be caused by infection at privileged (extrahepatic) sites, viral inhibition of antigen presentation, selective immune suppression, negative regulation of HCV gene expression, viral mutations, immune exhaustion of T cells and the incomplete differentiation of memory T cells [4,5].Fibrosis is the principal complication of chronic hepatitis C, and it is estimated that 20% of patients develop cirrhosis over a period of 10, 20 or 30 years [2,6]. The progression of fibrosis increases morbidity and mortality in chronic hepatitis C [7], since it can lead to death due to complications caused by cirrhosis or hepatocarcinoma [2].Various studies have associated the progression of fibrosis in hepatitis C with diverse factors such as: the kinetics and pathogenicity of HCV; host-HCV interaction; intrinsic host factors such as demographic profile, body mass index and diabetes mellitus; host exposure to external factors; and the form of HCV acquisition. Life Cycle and Pathogenicity of HCVBelonging to the Flaviviridae family, HCV is a small enveloped virus [8]. Its genome consists of one RNA molecule that is composed of two terminal regions, 5'-and 3'-untranslated regions, and between these there is a single open reading frame that encodes a polyprotein with approximately 3000 amino acids. This polyprotein cleaves at the N-terminal side of three structural proteins, the nucleocapsid (core), envelope 1 (E1) and envelope 2 (E2), all of which are involved in the architectural organization of HCV. At the carboxylterminal side, the polyprotein cleaves to six nonstructural proteins, NS2, NS3, NS4 (NS4A and NS4B), NS5 (NS5A and NS5B) and NS6, which are responsible for the life cycle of the virus [9].After entering a susceptible host, HCV invades, infects and replicates within the blood stream, repeating the process in various tissues, as well as in peripheral B and T lymphocytes, as it proceeds to the liver by tropism, passing through various tissues such as those of the pancreas, thyroid, adrenal glands, spleen and bone marrow [10][11][12]. Since HCV can also directly infect the lymphatic tissue, its stimulation can lead to the development of B-cell lymphomas [13]. It is known that the liver is the principal site of HCV replication, and various studies have shown that this virus infects approximately 10% of hepatic cells [5]. Infection with HCV at extrahepatic sites can promote the appearance of HCV variants [14,15], thereby decreasing the chance that the immune system will recognize the virus.To enter the host ...

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Immunopathogenesis of Hepatitis C Virus Infection: Multifaceted Strategies Subverting Innate and Adaptive Immunity

Abstract: Hepatitis C virus (HCV)

Cited by 72 publications

References 94 publications

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis

Viral clearance or persistence after acute hepatitis C infection: Interim results from a prospective study

Pathogenesis of hepatitis C: HCV consensus 2007

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