Hepatitis C virus infects T cells and affects interferon-γ signaling in T cell lines

Abstract It has been reported that hepatitis C virus (HCV) may infect and replicate in human T cells, particularly in perihepatic lymph nodes, but the extent and consequence of T-cell infection in patients is unclear. This study is conducted to characterize the parameters and functional consequences...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2007-04, Vol.361 (1), p.161-173
Main Authors: Kondo, Yasuteru, Sung, Vicky M.H, Machida, Keigo, Liu, Minyi, Lai, Michael M.C
Format: Article
Language:English
Subjects:
CD4
CD45RA
Cells, Cultured
Down-Regulation
HCV
Hepacivirus - growth & development
Hepatitis C virus
Hepatitis C, Chronic - immunology
Hepatitis C, Chronic - virology
Humans
Infectious Disease
Interferon-gamma - metabolism
Interferon-gamma - pharmacology
Lymphotropism
Phosphorylation
Recombinant Proteins
Signal Transduction - drug effects
STAT-1
STAT1 Transcription Factor - metabolism
T-bet
T-Box Domain Proteins - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - virology
Virus Cultivation
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Summary:Abstract It has been reported that hepatitis C virus (HCV) may infect and replicate in human T cells, particularly in perihepatic lymph nodes, but the extent and consequence of T-cell infection in patients is unclear. This study is conducted to characterize the parameters and functional consequences of HCV infection in T lymphocytes. By using a lymphotropic HCV strain, we showed that HCV could infect T cell lines (Molt-4 and Jurkat cells) in vitro. Both positive- and negative-strand HCV RNA were detected for several weeks after infection. Viral proteins could also be detected by immunofluorescence studies. Moreover, infectious HCV particles were produced from Molt-4 cell cultures, and could be used to infect naïve T cell lines. HCV could also infect human primary CD4+ T cells, particularly naïve (CD45RA+ CD45RO− ) CD4+ cells, in culture. The amounts of STAT-1 and phosphorylated STAT-1 proteins in the infected Molt-4 cells were significantly less than those in uninfected cultures, suggesting the possibility of defect in interferon-γ signaling. Indeed, T-bet and STAT-1 mRNA levels after interferon-γ stimulation in infected Molt-4 were suppressed. In conclusion, HCV could infect and transiently replicate in T cells and that HCV replication suppressed the IFN-γ/STAT-1/T-bet signaling due to the reduction of STAT-1 and inhibition of its activation (phosphorylation).
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2006.11.009