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Effects of the CCR5-Δ32 Mutation on Hepatitis C Virus-Specific Immune Responses in Patients with Haemophilia

Authors: Ahlenstiel, Golo (R18999); Woitas, Rainer P.; Iwan, Agathe; Nattermann, Jacob; Feldmann, Georg; Rockstroh, Jurgen K.; Oldenburg, Johannes; +3 Authors

Effects of the CCR5-Δ32 Mutation on Hepatitis C Virus-Specific Immune Responses in Patients with Haemophilia

Abstract

In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine receptor 5 (CCR5). Their recruitment to the liver is an important step in the immune response. A 32 base pair deletion in the CCR5 gene leads to reduced expression and total loss of CCR5 in CCR5-n32 heterozygous and homozygous subjects, respectively. However, the role of this mutation for antiviral immunity remains unclear. Here, we analysed proliferation, IFN-gamma and IL-4 secretion (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV-positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5 wildtype n = 10, CCR5-n32 heterozygous n = 5 and CCR5-n32 homozygous n = 6). Furthermore, T cell migration in response to the CCR5 ligands CCL3, -4 and -5 was studied. Overall IFN-gamma responses to HCV proteins were only slightly greater in CCR5 wild-type patients than in CCR5-n32 carriers (0.6 versus 0.24 SFC/10(4) PBMC; p = 0.043). This difference was consistently seen with all tested HCV antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4 production differed between CCR5 genotypes. Interruption of the CCR5 signalling pathway due to CCR5-n32 may potentially result in subtle reduction of HCV specific IFN-gamma responses in anti-HCV-positive haemophiliac patients.

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Keywords

hepatitis C virus, Adult, Male, 570, Receptors, CCR5, T-Lymphocytes, Hepacivirus, Viral Nonstructural Proteins, Hemophilia A, Lymphocyte Activation, immune response, Interferon-gamma, Cell Movement, hemophilia, XXXXXX - Unknown, Humans, Aged, Cell Proliferation, Sequence Deletion, Immunity, Cellular, Virulence, Hepatitis C, Chronic, Middle Aged, Hepatitis C, Chemotaxis, Leukocyte, Mutation, Female, Interleukin-4, Chemokines, Hepatitis C Antigens

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Average
Average
Top 10%