Respiratory syncytial virus matrix protein induces lung epithelial cell cycle arrest through a p53 dependent pathway.
Respiratory syncytial virus (RSV) is the major cause of viral respiratory infections in children. Our previous study showed that the RSV infection induced lung epithelial cell cycle arrest, which enhanced virus replication. To address the mechanism of RSV-induced cell cycle arrest, we examined the contribution of RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M protein caused the cells to proliferate at a slower rate than in control cells. The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549 cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M expression induced p53 and p21 accumulation and decreased phosphorylation of retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle arrest was restored after transfection of p53 cDNA into H1299 cells. Taken together, these results indicate that RSV-M protein regulates lung epithelial cell cycle through a p53-dependent pathway, which enhances RSV replication.
Laboratory of Respiratory Biology, National Institute of Environmental Human Science, Durham, North Carolina, United States of America.
Tao
T
Bian
John D
JD
Gibbs
Claes
C
Örvell
Farhad
F
Imani
D059447:Cell Cycle Checkpoints / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000821:virology; D008954:Models, Biological; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins