caa a22 4500 445889195 CHVBK 20180317145610.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00535-010-0297-2 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0297-2 Lymphotropic HCV strain can infect human primary naïve CD4+ cells and affect their proliferation and IFN-γ secretion activity [Elektronische Daten] [Yasuteru Kondo, Yoshiyuki Ueno, Eiji Kakazu, Koju Kobayashi, Masaaki Shiina, Keiichi Tamai, Keigo Machida, Jun Inoue, Yuta Wakui, Koji Fukushima, Noriyuki Obara, Osamu Kimura, Tooru Shimosegawa] 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 (2×104copies/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. Springer, 2010 HCV nationallicence Lymphotropic nationallicence Naïve CD4+ cell nationallicence Th1 nationallicence Kondo Yasuteru Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Ueno Yoshiyuki Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Kakazu Eiji Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Kobayashi Koju School of Health Science, Tohoku University, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Shiina Masaaki Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Tamai Keiichi Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Machida Keigo Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, 90033, Los Angeles, CA, USA aut Inoue Jun Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Wakui Yuta Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Fukushima Koji Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Obara Noriyuki Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Kimura Osamu Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Shimosegawa Tooru Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 232-241 0944-1174 46:2<232 2011 46 535 https://doi.org/10.1007/s00535-010-0297-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0297-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kondo Yasuteru Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Ueno Yoshiyuki Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Kakazu Eiji Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Kobayashi Koju School of Health Science, Tohoku University, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Shiina Masaaki Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Tamai Keiichi Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Machida Keigo Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Inoue Jun Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Wakui Yuta Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Fukushima Koji Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Obara Noriyuki Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Kimura Osamu Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 700 1- Shimosegawa Tooru Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, 980-8574, Sendai, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 232-241 0944-1174 46:2<232 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer