TY - JOUR
T1 - Lymphotropic HCV strain can infect human primary naïve CD4+ cells and affect their proliferation and IFN-γ secretion activity
AU - Kondo, Yasuteru
AU - Ueno, Yoshiyuki
AU - Kakazu, Eiji
AU - Kobayashi, Koju
AU - Shiina, Masaaki
AU - Tamai, Keiichi
AU - MacHida, Keigo
AU - Inoue, Jun
AU - Wakui, Yuta
AU - Fukushima, Koji
AU - Obara, Noriyuki
AU - Kimura, Osamu
AU - Shimosegawa, Tooru
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/2
Y1 - 2011/2
N2 - Background: Lymphotropic hepatitis C virus (HCV) infection of B and T cells might play an important role in the pathogenesis of hepatitis C. Recently, we showed that a lymphotropic HCV (SB strain) could infect established T-cell lines and B-cell lines. However, whether HCV replication interferes with cell proliferation and function in primary T lymphocytes is still unclear. Aim: The aim of this study was to analyze whether HCV replication in primary T lymphocytes affected their development, proliferation, and Th1 commitment. Methods: SB strain cell culture supernatant (2 × 104 copies/ml HCV) was used to infect several kinds of primary lymphocyte subsets. Mock, UV-irradiated SB-HCV, JFH-1 strain, and JFH-1 NS5B mutant, which could not replicate in T cells, were included as negative controls. Carboxyfluorescein succinimidyl ester (CFSE) and CD45RA double staining was used to evaluate the proliferative activity of CD4+CD45RA+CD45RO- naïve CD4+ cells. Interferon (IFN)-γ and interleukin (IL)-10 secretion assays magnetic cell sorting (MACS) were carried out. Results: Negative strand HCV RNA was detected in CD4+, CD14+, and CD19+ cells. Among CD4+ cells, CD4+CD45RA +RO- cells (naïve CD4+ cells) were most susceptible to replication of the SB strain. The levels of CFSE and CD45RA expression gradually declined during cell division in uninfected cells, while HCV-infected naïve CD4+ cells expressed higher levels of CFSE and CD45RA than Mock or UV-SB infected naïve CD4+ cells. Moreover, the production of IFN-γ was significantly suppressed in SB-infected naïve CD4+ cells. Conclusions: Lymphotropic HCV replication suppressed proliferation and development, including that towards Th1 commitment, in human primary naïve CD4+ cells.
AB - Background: Lymphotropic hepatitis C virus (HCV) infection of B and T cells might play an important role in the pathogenesis of hepatitis C. Recently, we showed that a lymphotropic HCV (SB strain) could infect established T-cell lines and B-cell lines. However, whether HCV replication interferes with cell proliferation and function in primary T lymphocytes is still unclear. Aim: The aim of this study was to analyze whether HCV replication in primary T lymphocytes affected their development, proliferation, and Th1 commitment. Methods: SB strain cell culture supernatant (2 × 104 copies/ml HCV) was used to infect several kinds of primary lymphocyte subsets. Mock, UV-irradiated SB-HCV, JFH-1 strain, and JFH-1 NS5B mutant, which could not replicate in T cells, were included as negative controls. Carboxyfluorescein succinimidyl ester (CFSE) and CD45RA double staining was used to evaluate the proliferative activity of CD4+CD45RA+CD45RO- naïve CD4+ cells. Interferon (IFN)-γ and interleukin (IL)-10 secretion assays magnetic cell sorting (MACS) were carried out. Results: Negative strand HCV RNA was detected in CD4+, CD14+, and CD19+ cells. Among CD4+ cells, CD4+CD45RA +RO- cells (naïve CD4+ cells) were most susceptible to replication of the SB strain. The levels of CFSE and CD45RA expression gradually declined during cell division in uninfected cells, while HCV-infected naïve CD4+ cells expressed higher levels of CFSE and CD45RA than Mock or UV-SB infected naïve CD4+ cells. Moreover, the production of IFN-γ was significantly suppressed in SB-infected naïve CD4+ cells. Conclusions: Lymphotropic HCV replication suppressed proliferation and development, including that towards Th1 commitment, in human primary naïve CD4+ cells.
KW - HCV
KW - Lymphotropic
KW - Naïve CD4 cell
KW - Th1
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U2 - 10.1007/s00535-010-0297-2
DO - 10.1007/s00535-010-0297-2
M3 - Article
C2 - 20714907
AN - SCOPUS:79954449418
VL - 46
SP - 232
EP - 241
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
IS - 2
ER -