Utilizing recombinant mRNA differential display a novel cDNA, termed Nebraska One (NEBR1), was cloned from HIV-1 infected monocyte- derived macrophages. NEBR1 functions as a transcriptional repressor with demonstrated anti-retroviral properties. Expressed copiously in HIV-1 infected mononuclear phagocytes (MP), NEBR1, could represent a unique innate immune. We hypothesize that NEBR1 is a natural cellular suppressor of HIV-1 that plays a role in both modulating macrophage function and viral infection during persistent disease. The relationship between NEBR1 and HIV-1 p24 expression in brain MP makes it of special interest to HIV-1 encephalitis and its associated dementia. To these ends we propose to elucidate: (1) the steps of HIV-1 life cycle in which NEBR1 suppresses HIV-1 replication (including HIV-1 entry, HIV-1 DNA synthesis, its genomic integration, and gene transcription from HIV DNA); (2) the DNA binding motif of NEBR1, and (3) the promoter/enhancer region(s) of NEBR1 that are activated by HIV-1. The intent of this proposal is to determine how NEBR1 is regulated and how it effects HIV-1 replication. The potential of NEBR1 to effect viral-host cell interactions is realistic, novel and contains therapeutic implications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI050894-01
Application #
6409066
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Miller, Roger H
Project Start
2001-07-01
Project End
2004-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$147,500
Indirect Cost
Name
University of Nebraska Medical Center
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
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Horiba, Masahide; Martinez, Lindsey B; Buescher, James L et al. (2007) OTK18, a zinc-finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions. J Gen Virol 88:236-41
Carlson, Kimberly A; Limoges, Jenae; Pohlman, Garrett D et al. (2004) OTK18 expression in brain mononuclear phagocytes parallels the severity of HIV-1 encephalitis. J Neuroimmunol 150:186-98
Carlson, Kimberly A; Leisman, Gary; Limoges, Jenae et al. (2004) Molecular characterization of a putative antiretroviral transcriptional factor, OTK18. J Immunol 172:381-91