Hepatitis C virus infection of T cells inhibits proliferation and enhances Fas-mediated apoptosis by down-regulating the expression of CD44 splicing variant 6

Yasuteru Kondo, Keigo Machida, Helene Minyi Liu, Yoshiyuki Ueno, Koju Kobayashi, Takaji Wakita, Tooru Shimosegawa, Michael M.C. Lai

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)726-736
Number of pages11
JournalJournal of Infectious Diseases
Volume199
Issue number5
DOIs
Publication statusPublished - 2009 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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