Document 0604
 DOCN  M9550604
 TI    Regulation of I kappa B alpha and p105 in monocytes and macrophages
       persistently infected with human immunodeficiency virus.
 DT    9505
 AU    McElhinny JA; MacMorran WS; Bren GD; Ten RM; Israel A; Paya CV;
       Department of Immunology, Mayo Clinic, Rochester, Minnesota; 55905.
 SO    J Virol. 1995 Mar;69(3):1500-9. Unique Identifier : AIDSLINE
       MED/95156575
 AB    The mechanisms regulating human immunodeficiency virus (HIV) persistence
       in human monocytes/macrophages are partially understood. Persistent HIV
       infection of U937 monocytic cells results in NF-kappa B activation.
       Whether virus-induced NF-kappa B activation is a mechanism that favors
       continuous viral replication in macrophages remains unknown. To further
       delineate the molecular mechanisms involved in the activation of
       NF-kappa B in HIV-infected monocytes and macrophages, we have focused on
       the regulation of the I kappa B molecules. First, we show that
       persistent HIV infection results in the activation of NF-kappa B not
       only in monocytic cells but also in macrophages. In HIV-infected cells,
       I kappa B alpha protein levels are decreased secondary to enhanced
       protein degradation. This parallels the increased I kappa B alpha
       synthesis secondary to increased I kappa B alpha gene transcription,
       i.e., increased RNA and transcriptional activity of its
       promoter-enhancer. Another protein with I kappa B function, p105, is
       also modified in HIV-infected cells: p105 and p50 steady-state protein
       levels are increased as a result of increased synthesis and proteolytic
       processing of p105. Transcriptional activity of p105 is also increased
       in infected cells and is also mediated by NF-kappa B through a specific
       kappa B motif. These results demonstrate the existence of a triple
       autoregulatory loop in monocytes and macrophages involving HIV, p105 and
       p50, and MAD3, with the end result of persistent NF-kappa B activation
       and viral persistence. Furthermore, persistent HIV infection of
       monocytes and macrophages provides a useful model with which to study
       concomitant modifications of different I kappa B molecules.
 DE    Base Sequence  Cell Line  DNA Primers/CHEMISTRY  Enhancer Elements
       (Genetics)  Gene Expression Regulation, Viral  Human  HIV
       Infections/*GENETICS  HIV-1/GENETICS  In Vitro
       Macrophages/*MICROBIOLOGY  Molecular Sequence Data
       Monocytes/*MICROBIOLOGY  NF-kappa B/*METABOLISM  Promoter Regions
       (Genetics)  Proto-Oncogene Proteins/*METABOLISM  RNA, Messenger/GENETICS
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Transcription,
       Genetic  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).