Hepatitis C virus infects T cells and affects interferon-gamma signaling in T cell lines.
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-gamma signaling. Indeed, T-bet and STAT-1 mRNA levels after interferon-gamma 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-gamma/STAT-1/T-bet signaling due to the reduction of STAT-1 and inhibition of its activation (phosphorylation).
Kondo
Yasuteru
Y
Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA. yasuteru@ebony.plala.or.jp
Sung
Vicky M H
VM
Machida
Keigo
K
Liu
Minyi
M
Lai
Michael M C
MM
D002478:Cells, Cultured; D015536:Down-Regulation; D016174:Hepacivirus / Q000254:growth & development*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014776:Virus Cultivation; D000098815:T-bet Transcription Factor
D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma