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Journal of Virology, November 2004, p. 11615-11621, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11615-11621.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cells Lacking NF-{kappa}B or in Which NF-{kappa}B Is Not Activated Vary with Respect to Ability To Sustain Herpes Simplex Virus 1 Replication and Are Not Susceptible to Apoptosis Induced by a Replication-Incompetent Mutant Virus

Brunella Taddeo,1 Weiran Zhang,1 Fred Lakeman,2 and Bernard Roizman1*

Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, Illinois,1 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama2

Received 28 April 2004/ Accepted 26 June 2004

Earlier we reported that NF-{kappa}B is activated by protein kinase R (PKR) in herpes simplex virus 1-infected cells. Here we report that in PKR–/– cells the yields of wild-type virus are 10-fold higher than in PKR+/+ cells. In cells lacking NF-{kappa}B p50 (nfkb1), p65 (relA), or both p50 and p65, the yields of virus were reduced 10-fold. Neither wild-type nor mutant cells undergo apoptosis following infection with wild-type virus. Whereas PKR+/+ and NF-{kappa}B+/+ control cell lines undergo apoptosis induced by the d120 ({Delta}{alpha}4) mutant of HSV-1, the mutant PKR–/– and NF-{kappa}B–/– cell lines were resistant. The evidence suggests that the stress-induced apoptosis resulting from d120 infection requires activation of NF-{kappa}B and that this proapoptotic pathway is blocked in cells in which NF-{kappa}B is not activated or absent. Activation of NF-{kappa}B in the course of viral infection may have dual roles of attempting to curtain viral replication by rendering the cell susceptible to apoptosis induced by the virus and by inducing the synthesis of proteins that enhance viral replication.

* Corresponding author. Mailing address: The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th St., Chicago, IL 60637. Phone: (773) 702-1898. Fax: (773) 702-1631. E-mail: Bernard.Roizman{at}bsd.uchicago.edu.

Journal of Virology, November 2004, p. 11615-11621, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11615-11621.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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