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Journal of Virology, May 1999, p. 3893-3903, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Ikappa kappa Mediates NF-kappa B Activation in Human Immunodeficiency Virus-Infected Cells

Susana Asin,1 Julie A. Taylor,1 Sergey Trushin,1 Gary Bren,1 and Carlos V. Paya1,2,*

Department of Immunology1 and Division of Infectious Diseases,2 Mayo Clinic, Rochester, Minnesota 55905

Received 16 September 1998/Accepted 27 January 1999

Human monocytes and macrophages are persistent reservoirs of human immunodeficiency virus (HIV) type-1. Persistent HIV infection of these cells results in increased levels of NF-kappa B in the nucleus secondary to increased Ikappa Balpha , Ikappa Bbeta , and Ikappa Bvarepsilon degradation, a mechanism postulated to regulate viral persistence. To characterize the molecular mechanisms regulating HIV-mediated degradation of Ikappa B, we have sought to identify the regulatory domains of Ikappa Balpha targeted by HIV infection. Using monocytic cells stably expressing different transdominant molecules of Ikappa Balpha , we determined that persistent HIV infection of these cells targets the NH2 but not the COOH terminus of Ikappa Balpha . Further analysis demonstrated that phosphorylation at S32 and S36 is necessary for HIV-dependent Ikappa Balpha degradation and NF-kappa B activation. Of the putative N-terminal Ikappa Balpha kinases, we demonstrated that the Ikappa kappa complex, but not p90rsk, is activated by HIV infection and mediates HIV-dependent NF-kappa B activation. Analysis of viral replication in cells that constitutively express Ikappa Balpha negative transdominant molecules demonstrated a lack of correlation between virus-induced NF-kappa B (p65/p50) nuclear translocation and degree of viral persistence in human monocytes.


* Corresponding author. Mailing address: Mayo Clinic, 200 First St. SW, Guggenheim 501, Rochester, MN 55905. Phone: (507) 284-3747. Fax: (507) 284-3757. E-mail: paya{at}mayo.edu.


Journal of Virology, May 1999, p. 3893-3903, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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