Document 0726
 DOCN  M95A0726
 TI    HIV-1 in the developing CNS: developmental differences in gene
       expression.
 DT    9510
 AU    Buzy JM; Lindstrom LM; Zink MC; Clements JE; Agency for International
       Development, USAID, Arlington, Virginia; 22209, USA.
 SO    Virology. 1995 Jul 10;210(2):361-71. Unique Identifier : AIDSLINE
       MED/95343548
 AB    HIV-1 infection of the CNS plays a direct role in the pathogenesis of
       AIDS dementia that frequently accompanies systemic AIDS. Both adult and
       pediatric AIDS are characterized by a high proportion of CNS disease.
       However, the pathogenic mechanisms responsible for AIDS dementia are not
       understood. A transgenic mouse model using the LTRs of two CNS-derived
       strains of HIV-1 (HIV-1JR-CSF and HIV-1JR-FL) has been developed to
       study HIV-1 gene expression in vivo. Analyses of expression in adult
       transgenic mice revealed expression in neurons in the CNS (J. R. Corboy,
       J. M. Buzy, M. C. Zink, and J. E. Clement, Science 258, 1804-1808,
       1992). In this study, developmental analyses of HIV-1-directed gene
       expression in embryonic and newborn transgenic mice derived from the
       above lines revealed strikingly different levels and patterns of
       expression in the CNS and spinal cord compared with adult mice.
       Increased expression was observed in the newborn brain compared to the
       adult, and the neuroanatomical pattern of expression was markedly
       different than that observed in adult brain. Transient expression was
       detected in the dorsal root ganglia and spinal cord in embryos and
       newborns up to Day 14. In contrast to the expression in neurons in adult
       CNS, HIV-1-directed gene expression in the newborn brain was observed in
       neurons, endothelial cells, and macrophages. This difference in
       expression during development probably reflects temporally regulated
       cellular transcription factors in the CNS. This transgenic model
       suggests that HIV-1 replication in the CNS may use cellular
       transcription factors different from those in nonneural tissues. Studies
       are in progress to identify cellular transcription factors that may be
       responsible for the differential expression of the LTRs.
 DE    beta-Galactosidase/BIOSYNTHESIS/GENETICS  Animal  Animals, Newborn  AIDS
       Dementia Complex/*VIROLOGY  Base Sequence  Central Nervous
       System/EMBRYOLOGY/*VIROLOGY  Comparative Study  Endothelium/VIROLOGY
       Eye/VIROLOGY  Gene Expression Regulation, Developmental/*PHYSIOLOGY
       Gene Expression Regulation, Viral/*PHYSIOLOGY  Genes, Reporter/GENETICS
       HIV Long Terminal Repeat/*GENETICS  HIV-1/*GENETICS/PHYSIOLOGY
       Macrophages/VIROLOGY  Mice  Mice, Transgenic  Microglia/VIROLOGY
       Molecular Sequence Data  Neurons/VIROLOGY  RNA, Messenger/ANALYSIS
       Support, U.S. Gov't, P.H.S.  Virus Replication  JOURNAL ARTICLE

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