       Document 0794
 DOCN  M9590794
 TI    The murine AIDS defective provirus acts as an insertional mutagen in its
       infected target B cells.
 DT    9509
 AU    Huang M; Takac M; Kozak CA; Jolicoeur P; Laboratory of Molecular
       Biology, Clinical Research Institute of; Montreal, Quebec, Canada.
 SO    J Virol. 1995 Jul;69(7):4069-78. Unique Identifier : AIDSLINE
       MED/95287456
 AB    In susceptible mice, the murine AIDS (MAIDS) defective virus can induce
       marked expansion of its target cells, the majority of which belong to
       the B-cell lineage. This expansion, which appears to be critical for the
       development of the immunodeficiency syndrome, is initially polyclonal
       but becomes oligoclonal late in the disease, suggesting the involvement
       of a secondary genetic event(s) during this proliferation. To determine
       whether integration of the MAIDS defective provirus into particular
       regions of the cellular genome contributes to this oligoclonal
       expansion, we searched for common provirus integration sites in enlarged
       lymphoid organs of MAIDS mice. We identified two common proviral
       integration sites, Dis-1 and Dis-2, which were occupied by a defective
       provirus at frequencies of 20 and 13%, respectively. Our analysis
       revealed that the Dis-1 region corresponds to the Sfpil1 (Spi-1, PU.1)
       locus, which maps on chromosome 2, and encodes a transcription factor.
       Insertion of the MAIDS defective provirus into this region led to a two-
       to threefold increase in the expression of Sfpi1 RNA. The Dis-2 locus
       was found to map to mouse chromosome 11, between Hox2 and Scya. It
       appears to be a novel locus probably harboring a gene involved in B-cell
       proliferation. The present study indicates that the MAIDS defective
       provirus can act as an insertional mutagen, thus contributing to the
       oligoclonal expansion of infected cells. The detection of two common
       proviral integration sites, each of which targetted at a low frequency
       in diseased organs, suggests that the deregulation of a unique gene
       through provirus insertion is essential for neither proliferation of
       infected B cells nor development of the immunodeficiency syndrome.
 DE    Animal  B-Lymphocytes/VIROLOGY  Chromosome Mapping  Cloning, Molecular
       Defective Viruses/*GENETICS  Leukemia Viruses, Murine/*GENETICS
       Lymphocyte Transformation  Mice  Mice, Inbred C57BL  Murine Acquired
       Immunodeficiency Syndrome/*VIROLOGY  *Mutagens  Proviruses/*GENETICS
       Repetitive Sequences, Nucleic Acid  RNA, Viral/ANALYSIS  Support,
       Non-U.S. Gov't  *Virus Integration  JOURNAL ARTICLE

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

