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Journal of Virology, December 2004, p. 13717-13726, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13717-13726.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Protein Kinase C-{alpha} Activity Is Required for Respiratory Syncytial Virus Fusion to Human Bronchial Epithelial Cells

Homero San-Juan-Vergara,1,2 Mark E. Peeples,3 Richard F. Lockey,1 and Shyam S. Mohapatra1,2*

The Joy McCann Culverhouse Airways Disease Research Center, Division of Allergy and Immunology, Department of Internal Medicine,1 Department of Medical Microbiology and Immunology, College of Medicine, University of South Florida, Tampa, Florida,2 Rush Medical College, Chicago, Illinois3

Received 9 February 2004/ Accepted 7 August 2004

Respiratory syncytial virus (RSV) infection activates protein kinase C (PKC), but the precise PKC isoform(s) involved and its role(s) remain to be elucidated. On the basis of the activation kinetics of different signaling pathways and the effect of various PKC inhibitors, it was reasoned that PKC activation is important in the early stages of RSV infection, especially RSV fusion and/or replication. Herein, the role of PKC-{alpha} during the early stages of RSV infection in normal human bronchial epithelial cells is determined. The results show that the blocking of PKC-{alpha} activation by classical inhibitors, pseudosubstrate peptides, or the overexpression of dominant-negative mutants of PKC-{alpha} in these cells leads to significantly decreased RSV infection. RSV induces phosphorylation, activation, and cytoplasm-to-membrane translocation of PKC-{alpha}. Also, PKC-{alpha} colocalizes with virus particles and is required for RSV fusion to the cell membrane. Thus, PKC-{alpha} could provide a new pharmacological target for controlling RSV infection.

* Corresponding author. Mailing address: The Joy McCann Culverhouse Airways Disease Research Center, Division of Allergy and Immunology, Department of Internal Medicine, MDC-19, 12901 Bruce B. Downs Blvd., Tampa, FL 33612. Phone: (813) 974-8574. Fax: (813) 974-8575. E-mail: smohapat{at}hsc.usf.edu.

Journal of Virology, December 2004, p. 13717-13726, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13717-13726.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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