Patient-derived hepatitis C virus inhibits CD4+ but not CD8+ T lymphocyte proliferation in primary T cells

Michalak, Tomasz I. and MacParland, Sonya Ann and Chen, Annie Y. and Corkum, Christopher P. and Pham, Tram Ngoc Quynh (2015) Patient-derived hepatitis C virus inhibits CD4+ but not CD8+ T lymphocyte proliferation in primary T cells. Virology Journal, 12 (93). ISSN 1743-422X

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Abstract

Background Hepatitis C virus (HCV) can replicate in cells of the immune system and productively propagate in primary T lymphocytes in vitro. We aimed to determine whether exposure to authentic, patient-derived HCV can modify the proliferation capacity, susceptibility to apoptosis and phenotype of T cells. Methods Primary total T cells from a healthy donor were used as targets and plasma-derived HCV from patients with chronic hepatitis C served as inocula. T cell phenotype was determined prior to and at different time points after exposure to HCV. T cell proliferation and apoptosis were measured by flow cytometry-based assays. Results The HCV inocula that induced the highest intracellular expression of HCV also caused a greatest shift in the T cell phenotype from predominantly CD4-positive to CD8-positive. This shift was associated with inhibition of CD4+ but not CD8+ T cell proliferation and did not coincide with altered apoptotic death of either cell subset. Conclusions The data obtained imply that exposure to native HCV can have an impact on the relative frequencies of CD4+ and CD8+ T cells by selectively suppressing CD4+ T lymphocyte proliferation and this may occur in both the presence and the absence of measurable HCV replication in these cells. If the virus exerts a similar effect in vivo, it may contribute to the impairment of virus-specific T cell response by altering cooperation between immune cell subsets.

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