Hepatitis C virus infection from the perspective of heterologous immunity

Cornberg, Markus; Wedemeyer, Heiner

doi:10.1016/j.coviro.2016.01.005

Cited by 21 publications

(29 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon activation, MAIT cells respond rapidly with cellular cytotoxicity as well as secretion of proinflammatory and anti-viral cytokines such * These authors contributed equally to this work. HCV is an extremely successful pathogen in that it establishes chronic infection in up to 90% of infected humans [9]. The reasons behind the failure of the human immune system to clear HCV are not fully understood but involve viral escape, CD4 and CD8 T-cell exhaustion, as well as NK-cell dysfunction [10][11][12] Until recently, pegylated IFN-α together with ribavirin was used to treat chronic HCV-infection.…”

Section: Mucosal-associated Invariant T (Mait) Cells Are T Cells Withmentioning

confidence: 99%

See 1 more Smart Citation

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

et al. 2016

Self Cite

View full text Add to dashboard Cite

Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction Mucosal-associated invariant T (MAIT) cells are T cells with innate-like characteristics enriched in human liver and at mucosalCorrespondence: Dr. Niklas K. Björkström e-mail: niklas.bjorkstrom@ki.se sites [1,2]. They express a semi-invariant TCR carrying the Vα7.2 segment together with a restricted Vβ repertoire [1,2]. Upon activation, MAIT cells respond rapidly with cellular cytotoxicity as well as secretion of proinflammatory and anti-viral cytokines such * These authors contributed equally to this work. HCV is an extremely successful pathogen in that it establishes chronic infection in up to 90% of infected humans [9]. The reasons behind the failure of the human immune system to clear HCV are not fully understood but involve viral escape, CD4 and CD8 T-cell exhaustion, as well as NK-cell dysfunction [10][11][12] Until recently, pegylated IFN-α together with ribavirin was used to treat chronic HCV-infection. However, pegylated IFN-α in doses administered to patients has direct inhibitory effects on immune cells [15][16][17][18]. In the last years, treatment of HCV has undergone a revolution with the introduction of highly effective direct-acting antivirals (DAA) that rapidly eliminate the virus [19]. Thus, today the vast majority of patients clear HCV after such IFN-free treatment regimens. This remarkable outcome allows for studies on consequences on immune cell recovery following rapid pathogen removal. In such studies, it was recently shown that both HCVspecific CD8 T cell and NK-cell populations become reinvigorated following viral clearance [20][21][22][23]. However, whether MAIT cells recover upon HCV clearance remains unclear.Here, we performed a comprehensive analysis of MAIT cells in chronic HCV-infection. Specifically, we addressed whether MAIT cell recovery occurs upon HCV-clearance in patients receiving an IFN-free treatment regimen consisting of sofosbuvir and ribavirin. Strikingly, and in contrast to other immune cells, MAIT cells were not reinvigorated following successful HCV-clearance using IFNfree therapy. The results are discussed in relation to the current knowledge on human MAIT cell responses to other viral infections and in the context of immune exhaustion during chronic infections. Results and discussion MAIT cells are among the most severely affected immune cells in chronic HCV-infectionTo determine the impact of chronic HCV-infection on the peripheral blood immune cell compartment, we assessed the major myeloid and lymphoid immune cell subsets in a cohort of HCVpatients and healthy donors by using a 23-parameter flow cytometry staining approach as previously described [24] (Supporting Information Fig. 1). The major phenotype observed in chronic HCV was a severe loss of MAIT cells (Fig. 1A, B). Other immune cell alterations noted were in line with previous studies, including an increase in Tregs [25], a reduced frequency of pDCs [26], and a shift within the CD4...

show abstract

Section: Mucosal-associated Invariant T (Mait) Cells Are T Cells Withmentioning

confidence: 99%

“…HCV is an extremely successful pathogen in that it establishes chronic infection in up to 90% of infected humans [9]. The reasons behind the failure of the human immune system to clear HCV are not fully understood but involve viral escape, CD4 and CD8 T-cell exhaustion, as well as NK-cell dysfunction [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Heterologous immunity and crossreactive CD8 T-cells in humans is associated with enhanced pathology such as dengue shock syndrome during DENV infection, necrotizing fulminant hepatitis during HCV infection, and acute infectious mononucleosis (AIM) during EBV-infection 1–3 . Although there are multiple mechanisms that can be involved in heterologous immunity, prior research in mice has shown that CD8 T-cell crossreactivity can mediate both beneficial and detrimental effects 1,4 .…”

Section: To the Editormentioning

confidence: 99%

“…Crossreactive responses are more likely to be detected where they contribute to illness and come to medical attention as in AIM. Investigators have reported apparent resistance to HIV or HCV infection in certain high-risk groups and detected circulating antigen-specific CD8 T-cells in these exposed, uninfected individuals 3,9 (see Materials and Methods). These HIV and HCV responses may be crossreactive memory responses 1 .…”

Section: To the Editormentioning

confidence: 99%

Unique influenza A cross-reactive memory CD8 T-cell receptor repertoire has a potential to protect against EBV seroconversion

Watkin

Mishra

Gil

et al. 2017

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Additional important polymorphisms are in the HLA locus. These may influence the outcome of infection through selection of immunodominant epitopes [43], cross-reactive responses [49], and interactions with natural killer cells [50]. …”

Section: The Host Response and The Outcome Of Hcv Infectionmentioning

confidence: 99%

Hepatitis C virus: life cycle in cells, infection and host response, and analysis of molecular markers influencing the outcome of infection and response to therapy

Dustin

Bartolini

Capobianchi

et al. 2016

Clinical Microbiology and Infection

View full text Add to dashboard Cite

Hepatitis C virus (HCV) is a major global health burden accounting for around 170 million chronic infections worldwide. Since its discovery, which dates back to about 30 years ago, many details of the viral genome organization and the astonishing genetic diversity have been unveiled but, owing to the difficulty of culturing HCV in vitro and obtaining fully susceptible yet immunocompetent in vivo models, we are still a long way from the full comprehension of viral life cycle, host cell pathways facilitating or counteracting infection, pathogenetic mechanisms in vivo, and host defenses. Here, we illustrate the viral life cycle into cells, describe the interplay between immune and genetic host factors shaping the course of infection, and provide details of the molecular approaches currently used to genotype, monitor replication in vivo, and studying the emergence of drug-resistant viral variants.

show abstract

Hepatitis C virus infection from the perspective of heterologous immunity

Cited by 21 publications

References 63 publications

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

Unique influenza A cross-reactive memory CD8 T-cell receptor repertoire has a potential to protect against EBV seroconversion

Hepatitis C virus: life cycle in cells, infection and host response, and analysis of molecular markers influencing the outcome of infection and response to therapy

Contact Info

Product

Resources

About