Growth arrest of epithelial cells during measles virus infection is caused by upregulation of interferon regulatory factor 1.
Natural infection with measles virus (MeV) is initiated when the virus reaches epithelial cells in the respiratory tract, oropharynx, or conjunctivae. Human epithelial cells infected with MeV frequently show growth suppression. In this study, we investigated the possible mechanisms for this suppression. The bronchiolar epithelial cell A549 showed growth arrest in G(0)/G(1) following MeV infection or treatment with gamma interferon (IFN-gamma). IFN regulatory factor-1 (IRF-1) was upregulated during MeV infection, although A549 did not produce IFN-gamma. Cells of the cervical squamous cell line SiHa persistently infected with various strains of MeV displayed slower growth than uninfected SiHa cells, although the growth rates varied depending on the MeV strain. Transfection of antisense-oriented IRF-1 cDNA released the MeV-infected SiHa cells from growth suppression. Although these infected cells did not produce IFN-gamma and suppressed IFN-alpha/beta-induced Jak1 phosphorylation, Jak1 was constitutively phosphorylated. The growth rates negatively correlated with levels of both IRF-1 expression and constitutively phosphorylated Jak1. These results indicate that MeV upregulates IRF-1 in a manner that is independent of IFN but dependent on the JAK/STAT pathway. This induction of IRF-1 appears to suppress cell growth, although the extent seems to vary among MeV strains.
Yokota
Shin-ichi
S
Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
Okabayashi
Tamaki
T
Yokosawa
Noriko
N
Fujii
Nobuhiro
N
D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1; D053613:Janus Kinase 1; D008459:Measles virus / Q000472:pathogenicity*; D010750:Phosphoproteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1