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J Virol, July 1998, p. 5610-5618, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Persistent Activation of RelA by Respiratory Syncytial Virus Involves Protein Kinase C, Underphosphorylated Ikappa Bbeta , and Sequestration of Protein Phosphatase 2A by the Viral Phosphoprotein

Vira Bitko and Sailen Barik*

Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, Alabama 36688-0002

Received 14 January 1998/Accepted 24 March 1998

Respiratory syncytial virus (RSV) activated the RelA (p65) subunit of nuclear factor kappa B (NF-kappa B) over many hours postinfection. The initial activation coincided with phosphorylation and degradation of Ikappa Balpha , the cytoplasmic inhibitor of RelA. During persistent activation of NF-kappa B at later times in infection, syntheses of inhibitors Ikappa Balpha as well as Ikappa Bbeta were restored. However, the resynthesized Ikappa Bbeta was in an underphosphorylated state, which apparently prevented inhibition of NF-kappa B. Use of specific inhibitors suggested that the pathway leading to the persistent---but not the initial---activation of NF-kappa B involved signaling through protein kinase C (PKC) and reactive oxygen intermediates of nonmitochondrial origin, whereas phospholipase C or D played little or no role. Thus, RSV infection led to the activation of NF-kappa B by a biphasic mechanism: a transient or early activation involving phosphorylation of the inhibitor Ikappa B polypeptides, and a persistent or long-term activation requiring PKC and the generation of hypophosphorylated Ikappa Bbeta . At least a part of the activation was through a novel mechanism in which the viral phosphoprotein P associated with but was not dephosphorylated by protein phosphatase 2A and thus sequestered and inhibited the latter. We postulate that this led to a net increase in the phosphorylation state of signaling proteins that are responsible for RelA activation.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, MSB 2140, College of Medicine, University of South Alabama, 307 University Blvd., Mobile, AL 36688-0002. Phone: (334) 460-6860. Fax: (334) 460-6127. E-mail: sbarik{at}jaguar1.usouthal.edu.

J Virol, July 1998, p. 5610-5618, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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