Serum antibodies against the hepatitis C virus E2 protein mediate antibody-dependent cellular cytotoxicity (ADCC)

Nattermann, Jacob; Schneiders, Angelika Maria; Leifeld, Ludger; Langhans, Bettina; Schulz, M.; Inchauspé, Geneviève; Matz, Bertfried; Brackmann, H.‐H.; Houghton, Michael; Sauerbruch, Tilman; Spengler, Ulrich

doi:10.1016/j.jhep.2004.12.018

Cited by 30 publications

(28 citation statements)

References 25 publications

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“…The role of antibody cytotoxic functions in HCV infection is still unclear. It was shown recently that serum antibodies against E2 from all stages of HCV infection could mediate ADCC (36). In our experiments designed to measure ADCC or CDC activity of HCV-AB 68 and HCV-AB 65, we could not observe any of these cytotoxic activities.…”

Section: Vol 80 2006 Neutralizing Human Monoclonal Antibodies Againmentioning

confidence: 57%

Preclinical Evaluation of Two Neutralizing Human Monoclonal Antibodies against Hepatitis C Virus (HCV): a Potential Treatment To Prevent HCV Reinfection in Liver Transplant Patients

Eren

Landstein

Terkieltaub

et al. 2006

J Virol

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Section: Vol 80 2006 Neutralizing Human Monoclonal Antibodies Againmentioning

confidence: 57%

Preclinical Evaluation of Two Neutralizing Human Monoclonal Antibodies against Hepatitis C Virus (HCV): a Potential Treatment To Prevent HCV Reinfection in Liver Transplant Patients

Eren

Landstein

Terkieltaub

et al. 2006

J Virol

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“…Anti-E2 antibodies are detected readily in patients with chronic hepatitis C [59] and, thus, hepatocytes bearing E2-anti-E2 complexes on their surface may become targets of ADCC (antibody-dependent cellular cytotoxicity) [60]. Antibody binding can occur independently from direct HCV infection of the cell.…”

Section: Interactions Of Hcv With the Tetraspanin Cd81mentioning

confidence: 99%

“…Such neutralizing antibodies could exert protective immunity [87], but occurred only infrequently in patients with self-limited HCV infection [84][85][86]. Finally, the antibody response and its effect on the evolution of HCV during chronic infection has also recently been linked to the level of liver injury [88], and anti-E2 antibodies with the capability to mediate liver damage via ADCC occur mainly only after a prolonged HCV infection [60]. Thus the precise contributions of natural HCV antibodies to viral elimination compared with liver damage and fibrosis progression still remain to be determined.…”

Section: Humoral Immunity In Chronic Hepatitis Cmentioning

confidence: 99%

Immunopathogenesis in hepatitis C virus cirrhosis

Spengler

Nattermann

2007

Clinical Science

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HCV (hepatitis C virus) has a high propensity to persist and to cause chronic hepatitis C, eventually leading to cirrhosis. Since HCV itself is not cytopathic, liver damage in chronic hepatitis C is commonly attributed to immune-mediated mechanisms. HCV proteins interact with several pathways in the host's immune response and disrupt pathogen-associated pattern recognition pathways, interfere with cellular immunoregulation via CD81 binding and subvert the activity of NK (natural killer) cells as well as CD4(+) and CD8(+) T-cells. Finally, HCV-specific T-cells become increasingly unresponsive and apparently disappear, owing to several possible mechanisms, such as escape mutations in critical viral epitopes, lack of sufficient help, clonal anergy or expansion of regulatory T-cells. The role of neutralizing antibodies remains uncertain, although it is still possible that humoral immunity contributes to bystander damage of virally coated cells via antibody-dependent cellular cytotoxicity. Cytotoxic lymphocytes kill HCV-infected cells via the perforin/granzyme pathway, but also release Fas ligand and inflammatory cytokines such as IFNgamma (interferon gamma). Release of soluble effector molecules helps to control HCV infection, but may also destroy uninfected liver cells and can attract further lymphocytes without HCV specificity to invade the liver. Bystander damage of these non-specific inflammatory cells will expand the tissue damage triggered by HCV infection and ultimately activate fibrogenesis. A clear understanding of these processes will eventually help to develop novel treatment strategies for HCV liver disease, independent from direct inhibition of HCV replication.

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“…It is demonstrated that spontaneous clearance of HCV occurs most often after the induction of an anti-HCV humoral immune response [42,43], indicating that antibodymediated immune responses, such as NK-ADCC, may contribute to the spontaneous clearance of HCV. Jacob et al demonstrate that specific antibodies to HCV E2 in serum can mediate ADCC activity, while the pathological mechanisms have not yet been studied in chronic HCV infection [44]. Alter et al stimulate NK cells with the P815-Ab antigen-antibody complex, and find that the proportion of IFN-γ-producing NK cells and CD107a-positive NK cells is lower in chronic HCV infected individuals than in subjects with spontaneous recovery from HCV infection [27].…”

Section: Journal Of Clinical and Cellular Immunologymentioning

confidence: 99%

Natural Killer Cells in HCV Infection

Lü¹,

Shen²

2017

J Clin Cell Immunol

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Natural killer (NK) cells play a vital role in controlling viral infection. This commentary will introduce the alteration of NK cells in different infected status involving frequencies, phenotypes and functions. Moreover, it highlights the function of antibody-dependent cell-mediated cytotoxicity (ADCC) in HCV and other virus infection, and concerns its role in vaccine development and immunotherapies.

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Serum antibodies against the hepatitis C virus E2 protein mediate antibody-dependent cellular cytotoxicity (ADCC)

Cited by 30 publications

References 25 publications

Preclinical Evaluation of Two Neutralizing Human Monoclonal Antibodies against Hepatitis C Virus (HCV): a Potential Treatment To Prevent HCV Reinfection in Liver Transplant Patients

Preclinical Evaluation of Two Neutralizing Human Monoclonal Antibodies against Hepatitis C Virus (HCV): a Potential Treatment To Prevent HCV Reinfection in Liver Transplant Patients

Immunopathogenesis in hepatitis C virus cirrhosis

Natural Killer Cells in HCV Infection

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