Hepatitis C: the complications of immune dysfunction

King, Ellis; Trabue, Christopher; Yin, Deling; Yao, Zhi Q.; Moorman, Jonathan P.

doi:10.1586/1744666x.3.2.145

Cited by 10 publications

(16 citation statements)

References 103 publications

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“…8,23 In this study, we found that the nucleocapsid core protein of HCV differentially regulates the functions of both B-and T-lymphocytes. This involved regulation of lymphocyte activation markers, effects on measures of cellular activation and alteration in adapter and kinase pathways fundamental to lymphocyte function.…”

Section: Discussionmentioning

confidence: 63%

“…This is manifest in several ways, including aberrant B-cell proliferation, decreased threshold for B-cell activation via the B-cell receptor complex, and overproduction of antibodies that are ineffective in controlling viral infection. 8 A non-neoplastic expansion of B-cell clones expressing immunoglobulin M (IgM) has been noted in mixed cryoglobulinemia, a process that can be observed in more than 50% of individuals chronically infected with HCV. It appears that whereas T-cell function is suppressed during chronic HCV infection, B cells often exhibit activation and clonal expansion.…”

Section: Introductionmentioning

confidence: 99%

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Differential regulation of SOCS‐1 signalling in B and T lymphocytes by hepatitis C virus core protein

et al. 2008

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SummaryHepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity, autoimmune phenomena and lymphomagenesis, supporting a role for lymphocyte dysregulation during persistent viral infection. We have shown that HCV core protein inhibits T-cell functions through interaction with a complement receptor, gC1qR. Here, we further report that B cells also express gC1qR that can be bound by HCV core protein. Importantly, using flow cytometry, we demonstrated differential regulation of B and T lymphocytes by the HCV core-gC1qR interaction, with down-regulation of CD69 activation in T cells but up-regulation of CD69 activation and cell proliferation in B cells. HCV core treatment led to decreased interferon-c production in CD8 + T cells but to increased immunoglobulin M and immunoglobulin G production as well as cell surface expression of costimulatory and chemokine receptors, including CD86 (B7-2), CD154 (CD40L) and CD195 (CCR5), in CD20 + B cells.Finally, we showed down-regulation of suppressor of cytokine signalling-1 (SOCS-1) using real-time reverse transcription-polymerase chain reaction, accompanied by up-regulation of signal transducer and activator of transcription-1 (STAT1) phosphorylation in B cells in response to HCV core protein, with the opposite pattern observed in HCV core-treated T cells. This study demonstrates differential regulation of B and T lymphocytes by HCV core and supports a mechanism by which lymphocyte dysregulation occurs in the course of persistent HCV infection.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Differential regulation of SOCS‐1 signalling in B and T lymphocytes by hepatitis C virus core protein

et al. 2008

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“…Consistent with prior studies, the most common non-AIDS-defining infection in our study was bacterial pneumonia 24–26 . Chronic viral hepatitis is known to be associated with dysregulation of hepatitis-specific immune responses, but further investigation is needed to explore potential mechanisms underlying an increased risk of bacterial infections 27,28 . Preventable infections such as influenza and pneumococcal pneumonia should be proactively addressed in PLWH with appropriate vaccinations to potentially reduce morbidity and hospitalizations 29,30 .…”

Section: Discussionmentioning

confidence: 99%

Impact of Hepatitis Coinfection on Hospitalization Rates and Causes in a Multicenter Cohort of Persons Living With HIV

Crowell¹,

Gebo²,

Balagopal³

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Chronic viral hepatitis is a potentially important determinant of healthcare utilization among persons living with HIV (PLWH). We describe hospitalization rates and reasons for hospitalization among PLWH stratified by co-infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Methods Laboratory, demographic, and hospitalization data were obtained for all patients receiving longitudinal HIV care during 2010 at 9 geographically diverse sites. Hepatitis serostatus was assessed by hepatitis B surface antigen and/or hepatitis C antibody. ICD-9 codes were used to assign hospitalizations into diagnostic categories. Negative binomial regression was used to assess factors associated with all-cause and diagnostic category-specific hospitalizations. Results A total of 2,793 hospitalizations were observed among 12,819 patients. Of these patients, 49.3% had HIV mono-infection, 4.1% HIV/HBV, 15.4% HIV/HCV, 2.5% HIV/HBV/HCV and 28.7% unknown hepatitis serostatus. Compared to HIV mono-infection, risk of all-cause hospitalization was increased with HIV/HBV (adjusted incidence rate ratio (aIRR) 1.55 [1.17–2.06]), HIV/HCV (1.45 [1.21–1.74]) and HIV/HBV/HCV (1.52 [1.04–2.22]). Risk of hospitalization for non-AIDS-defining infection was also higher among patients with HIV/HBV (2.07 [1.38–3.11]), HIV/HCV (1.81 [1.36–2.40]) and HIV/HBV/HCV (1.96 [1.11–3.46]). HIV/HBV was associated with hospitalization for gastrointestinal/liver disease (2.55 [1.30–5.01]). HIV/HCV was associated with hospitalization for psychiatric illness (1.89 [1.11–3.26]). Conclusions HBV and HCV co-infection are associated with increased risk of all-cause hospitalization and hospitalization for non-AIDS-defining infections, as compared to HIV mono-infection. Policy-makers and third-party payers should be aware of the heightened risk of hospitalization associated with co-infection when allocating healthcare resources and considering models of healthcare delivery.

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“…Hepatitis C virus (HCV) infects over 180 million people worldwide and exhibits a remarkable propensity toward chronic hepatitis, liver cirrhosis and hepatocellular carcinoma1. Chronic HCV infection is also associated with B cell lymphoproliferative disorders2, including most notably mixed cryoglobulinemia (MC) and B cell lymphomas.…”

Section: Introductionmentioning

confidence: 99%

PD‐1 modulates regulatory T cells and suppresses T‐cell responses in HCV‐associated lymphoma

Cheng²,

Zhang³

et al. 2010

Immunol Cell Biol

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T regulatory (TR) cells suppress T cell responses that are critical in the development of chronic viral infection and associated malignancies. Programmed death-1 (PD-1) also plays a pivotal role in regulation of T cell functions during chronic viral infection. To examine the role of PD-1 pathway in regulating TR cell functions that inhibit T cell responses during virus-associated malignancy, TR cells were investigated in the setting of hepatitis C virus-associated lymphoma (HCV-L), non-HCV-associated lymphoma (non-HCV-L), HCV infection alone, and healthy subjects (HS). Relatively high numbers of CD4+CD25+ and CD8+CD25+ TR cells as well as high levels of PD-1 expressions on these TR cells were found in the peripheral blood of subjects with HCV-L compared to those from non-HCV-L or HCV alone or HS. TR cells from the HCV-L subjects were capable of suppressing the autogeneic lymphocyte response, and depletion of TR cells in PBMC from HCV-L improved T cell proliferation. Additionally, the suppressed T cell activation and proliferation in HCV-L was partially restored by blocking the PD-1 pathway ex vivo, resulting in both a reduction in TR cell number and the ability of TR to suppress the activity of effector T cells. This study suggests that the PD-1 pathway is involved in regulating TR cells that suppress T cell functions in the setting of HCV-associated B cell lymphoma.

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Hepatitis C: the complications of immune dysfunction

Cited by 10 publications

References 103 publications

Differential regulation of SOCS‐1 signalling in B and T lymphocytes by hepatitis C virus core protein

Differential regulation of SOCS‐1 signalling in B and T lymphocytes by hepatitis C virus core protein

Impact of Hepatitis Coinfection on Hospitalization Rates and Causes in a Multicenter Cohort of Persons Living With HIV

PD‐1 modulates regulatory T cells and suppresses T‐cell responses in HCV‐associated lymphoma

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