proposal) Macrophages play a key role in the pathogenesis of HIV infection, in that they serve as a main reservoir of persistent viral replication throughout the infection. However, the mechanisms regulating viral persistence remain uncharacterized. The NF-kB/rel family of transcription factors is essential for HIV transcription and replication in macrophages. NF-kB activity is constitutive in the nuclei of macrophages, in the form of RelB, and exists as a cytosolic and inducible pool of NF-kB (p50/65) associated with IkB. Studies from this lab have identified components of NF-kB that are unique to macrophages, this includes the targeting of IkBa and nuclear translocation of NF-kB following HIV infection. This process is regulated by induced kinases that phosphorylate IkBa at S32/36. These workers have identified an inducible IkBa kinase in macrophages, casein kinase II (PK-CK2). The primary goal of the proposal is to characterize the molecular mechanisms whereby NF-kB participates in the regulation of HIV persistence in human macrophages.
The aims are: 1) to characterize the molecular composition and regulation of constitutive NF-kB (RelB) activity and its relevance to virus replication; 2) to study the mechanisms of HIV-dependent activation of the induced pool of NF-kB through IkBa targeting; and 3) to characterize the function of the inducible IkBa kinase and the relationship to PK-CK2.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036076-06
Application #
2886919
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Plaeger, Susan F
Project Start
1994-08-01
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
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