Adaptive immune response during hepatitis C virus infection

Larrubia, J.R.; Moreno-Cubero, Elia; Lokhande, M.U.; García-Garzón, Silvia; Lázaro, Alicia; Míquel, J.; Perna, Cristian; Sanz-de-Villalobos, E.

doi:10.3748/wjg.v20.i13.3418

Cited by 63 publications

(50 citation statements)

References 107 publications

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“…However, the HCV-specific T cell immune response is critical for the control of HCV infection and HCV clearance (44,45). A case report indicated that HCV-specific CD4 + T cell responses are weak in chronic HCV infection (46).…”

Section: Discussionmentioning

confidence: 99%

MCPIP1 Suppresses Hepatitis C Virus Replication and Negatively Regulates Virus-Induced Proinflammatory Cytokine Responses

Lin

Chu

Chien

et al. 2014

The Journal of Immunology

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Human MCP-1–induced protein 1 (MCPIP1, also known as ZC3H12A and Regnase-1) plays important roles in negatively regulating the cellular inflammatory response. Recently, we found that as an RNase, MCPIP1 has broad-spectrum antiviral effects by targeting viral RNA. In this study, we demonstrated that MCPIP1 expression was induced by hepatitis C virus (HCV) infection in Huh7.5 hepatoma cells. MCPIP1 expression was higher in liver tissue from patients with chronic HCV infection compared with those without chronic HCV infection. Knockdown of MCPIP1 increased HCV replication and HCV-mediated expression of proinflammatory cytokines, such as TNF-α, IL-6, and MCP-1. However, overexpression of MCPIP1 significantly inhibited HCV replication and HCV-mediated expression of proinflammatory cytokines. Various mutants of functional domains of MCPIP1 showed disruption of the RNA binding and oligomerization abilities, as well as RNase activity, but not deubiquitinase activity, which impaired the inhibitory activity against HCV replication. On immunocytochemistry, MCPIP1 colocalized with HCV RNA. Use of a replication-defective HCV John Cunningham 1/AAG mutant and in vitro RNA cleavage assay demonstrated that MCPIP1 could directly degrade HCV RNA. MCPIP1 may suppress HCV replication and HCV-mediated proinflammatory responses with infection, which might contribute to the regulation of host defense against the infection and virus-induced inflammation.

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Section: Discussionmentioning

confidence: 99%

MCPIP1 Suppresses Hepatitis C Virus Replication and Negatively Regulates Virus-Induced Proinflammatory Cytokine Responses

Lin

Chu

Chien

et al. 2014

The Journal of Immunology

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“…EBV produces a regulatory cytokine that is nearly indistinguishable from human IL-10 [36,37]. In response to attack by T cells, pathogens such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have been demonstrated to avoid T-cell mediated response by the deletion of Teff epitopes [38][39][40].…”

Section: Tcr Degeneracy Epitope Redundancy Mimicry and Camouflagementioning

confidence: 99%

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

Moise

Beseme

Tassone

et al. 2016

Expert Review of Vaccines

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SummaryT cells are extensively trained on 'self' in the thymus and then move to the periphery, where they seek out and destroy infections and regulate immune response to self-antigens. T cell receptors (TCR) on T cells' surface recognize T cell epitopes, short linear strings of amino acids presented by antigen-presenting cells. Some of these epitopes activate T effectors, while others activate regulatory T cells. It was recently discovered that T cell epitopes that are highly conserved on their TCR face with human genome sequences are often associated with T cells that regulate immune response. These TCR-cross-conserved or 'redundant epitopes' are more common in proteins found in pathogens that have co-evolved with humans than in other noncommensal pathogens. Epitope redundancy might be the link between pathogens and autoimmune disease. This article reviews recently published data and addresses epitope redundancy, the "elephant in the room" for vaccine developers and T cell immunologists.

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“…This process, known as "deimmunization" in the biologics industry, has been observed in the course of infection by RNA viruses (HIV, HCV [23][24][25] ). Evaluations of total T cell epitope content in bacterial genomes appear to confirm that deimmunization may also occur in selected bacteria.…”

Section: Defense Against Adaptive Immune Responsementioning

confidence: 99%

Immune camouflage: Relevance to vaccines and human immunology

Groot

Moise

et al. 2014

Human Vaccines & Immunotherapeutics

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High strain sequence variability, interference with innate immune mechanisms, and epitope deletion are all examples of strategies that pathogens have evolved to subvert host defenses. To this list we would add another strategy: immune camouflage. Pathogens whose epitope sequences are cross-conserved with multiple human proteins at the TCR-facing residues may be exploiting “ignorance and tolerance," which are mechanisms by which mature T cells avoid immune responses to self-antigens. By adopting amino acid configurations that may be recognized by autologous regulatory T cells, pathogens may be actively suppressing protective immunity. Using the new JanusMatrix TCR-homology-mapping tool, we have identified several such ‘camouflaged’ tolerizing epitopes that are present in the viral genomes of pathogens such as emerging H7N9 influenza. Thus in addition to the overall low number of T helper epitopes that is present in H7 hemaglutinin (as described previously, see http://dx.doi.org/10.4161/hv.24939), the presence of such tolerizing epitopes in H7N9 could explain why, in recent vaccine trials, whole H7N9-HA was poorly immunogenic and associated with low seroconversion rates (see http://dx.doi.org/10.4161/hv.28135). In this commentary, we provide an overview of the immunoinformatics process leading to the discovery of tolerizing epitopes in pathogen genomic sequences, provide a brief summary of laboratory data that validates the discovery, and point the way forward. Removal of viral, bacterial and parasite tolerizing epitopes may permit researchers to develop more effective vaccines and immunotherapeutics in the future.

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Adaptive immune response during hepatitis C virus infection

Cited by 63 publications

References 107 publications

MCPIP1 Suppresses Hepatitis C Virus Replication and Negatively Regulates Virus-Induced Proinflammatory Cytokine Responses

MCPIP1 Suppresses Hepatitis C Virus Replication and Negatively Regulates Virus-Induced Proinflammatory Cytokine Responses

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

Immune camouflage: Relevance to vaccines and human immunology

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