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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.
I
Mediates NF-
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-
B in the nucleus secondary
to increased I
B
, I
B
, and I
B
degradation, a mechanism postulated to regulate viral persistence. To characterize the molecular
mechanisms regulating HIV-mediated degradation of I
B, we have sought
to identify the regulatory domains of I
B
targeted by HIV
infection. Using monocytic cells stably expressing different transdominant molecules of I
B
, we determined that persistent HIV
infection of these cells targets the NH2 but not the COOH terminus of I
B
. Further analysis demonstrated that
phosphorylation at S32 and S36 is necessary for
HIV-dependent I
B
degradation and NF-
B activation. Of the
putative N-terminal I
B
kinases, we demonstrated that the I
complex, but not p90rsk, is activated by HIV
infection and mediates HIV-dependent NF-
B activation. Analysis of
viral replication in cells that constitutively express I
B
negative transdominant molecules demonstrated a lack of correlation
between virus-induced NF-
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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