BACKGROUND: A lymphotropic hepatitis C virus strain (HCV, SB strain, hereafter "SB-HCV") has been shown to infect established T cell lines (Molt-4 and Jurkat) and primary human naive CD4(+) T cells. During T cell development and activation, transient expression of CD44 splicing variant 6 (CD44v6) plays a significant role. METHODS: SB-HCV was used to infect Molt-4 cells, and their cellular proliferation and CD44 expression was examined. RESULTS: SB-HCV-infected Molt-4 cells expressed a significantly lower level of the CD44v6 isoform. The infected cells could be divided into 2 carboxyfluorescein succinimidyl ester (CFSE) groups, CFSE-high (indicating low proliferation activity; 34.2% of the cells) and CFSE-low (indicating high proliferation activity; 62.5% of the cells), whereas uninfected cells consisted of only a CFSE-low population. Of the CFSE-high cells, 82.4% were positive for the HCV protein NS5A, whereas only 1.2% of the CFSE-low cells were positive for this protein. Among the HCV proteins, NS5A alone caused the down-regulation of CD44v6 expression. After cells were stimulated with phorbol myristate acetate, the amount of phosphorylated mitogen-activated protein (MAP) kinase was significantly reduced in CFSE-high, SB-HCV-infected Molt-4 cells. After Fas ligand stimulation, SB-HCV-infected Molt-4 cells had increased cleavage of caspase 8 and 3 and enhanced apoptosis, compared with the rates of cleavage and apoptosis in control groups, indicating that SB-HCV infection increased Fas-mediated apoptosis. CONCLUSION: HCV replication in T cells suppresses cellular proliferation and enhances susceptibility to Fas signaling by inhibiting CD44v6 signaling and expression.
BACKGROUND: A lymphotropic hepatitis C virus strain (HCV, SB strain, hereafter "SB-HCV") has been shown to infect established T cell lines (Molt-4 and Jurkat) and primary human naive CD4(+) T cells. During T cell development and activation, transient expression of CD44 splicing variant 6 (CD44v6) plays a significant role. METHODS: SB-HCV was used to infect Molt-4 cells, and their cellular proliferation and CD44 expression was examined. RESULTS: SB-HCV-infected Molt-4 cells expressed a significantly lower level of the CD44v6 isoform. The infected cells could be divided into 2 carboxyfluorescein succinimidyl ester (CFSE) groups, CFSE-high (indicating low proliferation activity; 34.2% of the cells) and CFSE-low (indicating high proliferation activity; 62.5% of the cells), whereas uninfected cells consisted of only a CFSE-low population. Of the CFSE-high cells, 82.4% were positive for the HCV protein NS5A, whereas only 1.2% of the CFSE-low cells were positive for this protein. Among the HCV proteins, NS5A alone caused the down-regulation of CD44v6 expression. After cells were stimulated with phorbol myristate acetate, the amount of phosphorylated mitogen-activated protein (MAP) kinase was significantly reduced in CFSE-high, SB-HCV-infected Molt-4 cells. After Fas ligand stimulation, SB-HCV-infected Molt-4 cells had increased cleavage of caspase 8 and 3 and enhanced apoptosis, compared with the rates of cleavage and apoptosis in control groups, indicating that SB-HCV infection increased Fas-mediated apoptosis. CONCLUSION: HCV replication in T cells suppresses cellular proliferation and enhances susceptibility to Fas signaling by inhibiting CD44v6 signaling and expression.
Authors: Jin Zhong; Pablo Gastaminza; Guofeng Cheng; Sharookh Kapadia; Takanobu Kato; Dennis R Burton; Stefan F Wieland; Susan L Uprichard; Takaji Wakita; Francis V Chisari Journal: Proc Natl Acad Sci U S A Date: 2005-06-06 Impact factor: 11.205
Authors: Keigo Machida; Yasuteru Kondo; Jeffrey Y Huang; Yung-Chia Chen; Kevin T-H Cheng; Zhenyong Keck; Steven Foung; Jean Dubuisson; Vicky M-H Sung; Michael M C Lai Journal: J Virol Date: 2008-04-16 Impact factor: 5.103
Authors: Thijs Feuth; Joop E Arends; Justin H Fransen; Nening M Nanlohy; Karel J van Erpecum; Peter D Siersema; Andy I M Hoepelman; Debbie van Baarle Journal: PLoS One Date: 2013-03-15 Impact factor: 3.240