Effects of the CCR5-Δ32 Mutation on Hepatitis C Virus-Specific Immune Responses in Patients with Haemophilia
Effects of the CCR5-Δ32 Mutation on Hepatitis C Virus-Specific Immune Responses in Patients with Haemophilia
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.
- University of Bonn Germany
- Western Sydney University Australia
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
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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