GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Differential virus‐specific CD 8 + T‐cell epitope repertoire in hepatitis C virus genotype 1 versus 4
    Wiley ; 2018
    In:  Journal of Viral Hepatitis Vol. 25, No. 7 ( 2018-07), p. 779-790
    Details
    In: Journal of Viral Hepatitis, Wiley, Vol. 25, No. 7 ( 2018-07), p. 779-790
    Abstract: Virus‐specific CD 8 + T‐cell responses play an important role in the outcome of hepatitis C virus ( HCV ) infection. To date, most HCV ‐specific CD 8 + T‐cell epitopes have been defined in HCV genotype 1 infection. In contrast, the HCV genotype 4‐specific CD 8 + T‐cell response is poorly defined. Here, we analysed whether known HCV ‐specific CD 8 + T‐cell epitopes are also recognized in HCV genotype 4‐infected patients and set out to identify the first HCV genotype 4‐specific CD 8 + T‐cell epitopes. We studied patients chronically infected with HCV genotype 1 (n = 20) or 4 (n = 21) using 91 well‐described HCV ‐specific epitope peptides. In addition, we analysed 24 genotype 4‐infected patients using 40 epitope candidates predicted using an in silico approach. HCV ‐specific CD 8 + T‐cell responses targeting previously described epitopes were detectable in the majority of genotype 1‐infected patients (11 of 20). In contrast, patients infected with HCV genotype 4 rarely targeted these epitopes (4 of 21; P  = .0247). Importantly, we were able to identify eight novel HCV genotype 4‐specific CD 8 + T‐cell epitopes. Only one of these epitopes was shared between genotype 1 and genotype 4. These results indicate that there is little overlap between CD 8 + T‐cell repertoires targeting HCV genotype 1 and 4. Prophylactic vaccination studies based on HCV genotype 1 are currently underway. However, in countries with the highest prevalence of HCV infection, such as Egypt, most patients are infected with HCV genotype 4. Thus, prophylactic vaccination strategies need to be adapted to HCV genotype 4 before their application to regions where HCV genotype 4 is endemic.
    Type of Medium: Online Resource
    ISSN: 1352-0504 , 1365-2893
    URL: Issue
    URL: Article
    DOI: 10.1111/jvh.2018.25.issue-7
    DOI: 10.1111/jvh.12874
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2007924-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    HCV-Specific T Cell Responses During and After Chronic HCV Infection
    MDPI AG ; 2018
    In:  Viruses Vol. 10, No. 11 ( 2018-11-17), p. 645-
    Details
    In: Viruses, MDPI AG, Vol. 10, No. 11 ( 2018-11-17), p. 645-
    Abstract: Hepatitis C virus (HCV)-specific T cell responses are closely linked to the clinical course of infection. While T cell responses in self-limiting infection are typically broad and multi-specific, they display several distinct features of functional impairment in the chronic phase. Moreover, HCV readily adapts to immune pressure by developing escape mutations within epitopes targeted by T cells. Much of our current knowledge on HCV-specific T cell responses has been gathered under the assumption that this might eventually pave the way for a therapeutic vaccine. However, with the development of highly efficient direct acting antivirals (DAAs), there is less interest in the development of a therapeutic vaccine for HCV and the scope of T cell research has shifted. Indeed, the possibility to rapidly eradicate an antigen that has persisted over years or decades, and has led to T cell exhaustion and dysfunction, provides the unique opportunity to study potential T cell recovery after antigen cessation in a human in vivo setting. Findings from such studies not only improve our basic understanding of T cell immunity but may also advance immunotherapeutic approaches in cancer or chronic hepatitis B and D infection. Moreover, in order to edge closer to the WHO goal of HCV elimination by 2030, a prophylactic vaccine is clearly required. Thus, in this review, we will summarize our current knowledge on HCV-specific T cell responses and also provide an outlook on the open questions that require answers in this field.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v10110645
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2516098-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Virushepatitis – wann daran denken?
    Georg Thieme Verlag KG ; 2019
    In:  DMW - Deutsche Medizinische Wochenschrift Vol. 144, No. 08 ( 2019-04), p. 520-527
    Details
    In: DMW - Deutsche Medizinische Wochenschrift, Georg Thieme Verlag KG, Vol. 144, No. 08 ( 2019-04), p. 520-527
    Abstract: Chronic viral hepatitis can remain unrecognized but may nevertheless lead to liver cirrhosis and hepatocellular carcinoma. Thus, patients with elevated liver enzymes as well as risk groups need to be screened and treated for viral hepatitis. These groups include, in particular, migrants from countries with high HBV or HCV prevalence, persons with previous or current intravenous drug use, and homosexual men. For HBV- or HCV-associated diseases, such as panarteriitis nodosa, cryoglobulinemic vasculitis or B-cell lymphoma, antiviral therapy may lead to remission. Prior to high-dose immunosuppressive therapy, especially with regimes containing rituximab, chronic or resolved HBV infection must be ruled out or antiviral prophylaxis may be required to avoid a potentially fatal HBV reactivation.
    Type of Medium: Online Resource
    ISSN: 0012-0472 , 1439-4413
    URL: Article
    DOI: 10.1055/a-0640-3627
    RVK:
    XA 39100
    RVK:
    XA 10000
    Language: German
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2019
    detail.hit.zdb_id: 2035474-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load
    BMJ ; 2019
    In:  Gut Vol. 68, No. 5 ( 2019-05), p. 905-915
    Details
    In: Gut, BMJ, Vol. 68, No. 5 ( 2019-05), p. 905-915
    Abstract: A hallmark of chronic HBV (cHBV) infection is the presence of impaired HBV-specific CD8+ T cell responses. Functional T cell exhaustion induced by persistent antigen stimulation is considered a major mechanism underlying this impairment. However, due to their low frequencies in chronic infection, it is currently unknown whether HBV-specific CD8+ T cells targeting different epitopes are similarly impaired and share molecular profiles indicative of T cell exhaustion. Design By applying peptide-loaded MHC I tetramer-based enrichment, we could detect HBV-specific CD8+ T cells targeting epitopes in the HBV core and the polymerase proteins in the majority of 85 tested cHBV patients with low viral loads. Lower detection rates were obtained for envelope-specific CD8+ T cells. Subsequently, we performed phenotypic and functional in-depth analyses. Results HBV-specific CD8+ T cells are not terminally exhausted but rather exhibit a memory-like phenotype in patients with low viral load possibly reflecting weak ongoing cognate antigen recognition. Moreover, HBV-specific CD8+ T cells targeting core versus polymerase epitopes significantly differed in frequency, phenotype and function. In particular, in comparison with core-specific CD8+ T cells, a higher frequency of polymerase-specific CD8+ T cells expressed CD38, KLRG1 and Eomes accompanied by low T-bet expression and downregulated CD127 indicative of a more severe T cell exhaustion. In addition, polymerase-specific CD8+ T cells exhibited a reduced expansion capacity that was linked to a dysbalanced TCF1/BCL2 expression. Conclusions Overall, the molecular mechanisms underlying impaired T cell responses differ with respect to the targeted HBV antigens. These results have potential implications for immunotherapeutic approaches in HBV cure.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2018-316641
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 1492637-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    FRI-138-HBVcore-versus HBVpolymerase-specific CD8+ T cells differ in chronically HBV-infected patients
    Elsevier BV ; 2019
    In:  Journal of Hepatology Vol. 70, No. 1 ( 2019-04), p. e448-
    Details
    In: Journal of Hepatology, Elsevier BV, Vol. 70, No. 1 ( 2019-04), p. e448-
    Type of Medium: Online Resource
    ISSN: 0168-8278
    URL: Article
    DOI: 10.1016/S0618-8278(19)30883-7
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2027112-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C
    S. Karger AG ; 2016
    In:  Digestive Diseases Vol. 34, No. 4 ( 2016), p. 396-409
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 34, No. 4 ( 2016), p. 396-409
    Abstract: Approximately 500 million people are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) worldwide and are thus at high risk of progressive liver disease, leading to liver fibrosis, cirrhosis and ultimately hepatocellular cancer. Virus-specific CD8+ T-cells play a major role in viral clearance in 〉 90% of adult patients who clear HBV and in approximately 30% of patients who clear HCV in acute infection. However, several mechanisms contribute to the failure of the adaptive CD8+ T-cell response in those patients who progress to chronic infection. These include viral mutations leading to escape from the CD8+ T-cell response as well as exhaustion and dysfunction of virus-specific CD8+ T-cells. Antiviral efficacy of the virus-specific CD8+ T-cell response also strongly depends on its restriction by specific human leukocyte antigens (HLA) class I alleles. Our review will summarize the role of HLA-A, B and C-restricted CD8+ T-cells in HBV and HCV infection. Due to the current lack of a comprehensive database of HBV- and HCV-specific CD8+ T-cell epitopes, we also provide a summary of the repertoire of currently well-described HBV- and HCV-specific CD8+ T-cell epitopes. A better understanding of the factors that contribute to the success or failure of virus-specific CD8+ T-cells may help to develop new therapeutic options for HBV eradication in patients with chronic HBV infection (therapeutic vaccination and/or immunomodulation) as well as a prophylactic vaccine against HCV infection.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000444555
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 1482221-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...