Document 0420
 DOCN  M9490420
 TI    Myristylation of Pr60gag of the murine AIDS-defective virus is required
       to induce disease and notably for the expansion of its target cells.
 DT    9411
 AU    Huang M; Jolicoeur P; Laboratory of Molecular Biology, Clinical Research
       Institute of; Montreal, Quebec, Canada.
 SO    J Virol. 1994 Sep;68(9):5648-55. Unique Identifier : AIDSLINE
       MED/94335078
 AB    Murine AIDS (MAIDS) is characterized by severe lymphadenopathy and
       splenomegaly. The proliferation of the infected target B cells is also
       an important manifestation of the disease (M. Huang, C. Simard, D. G.
       Kay, and P. Jolicoeur, J. Virol. 65:6562-6571, 1991). The etiologic
       agent of MAIDS is a defective murine leukemia virus that is deleted of
       most of its pol and env genes and appears to encode a single protein,
       the Gag precursor Pr60gag protein. Pr60gag is myristylated and attached
       to the plasma membrane. To study the role myristylation on the function
       of Pr60gag, we have generated a myristylation-negative (Myr-) mutant of
       the MAIDS defective virus. We found that Myr- Pr60gag interacted less
       tightly with the plasma membrane. In addition, the Myr- MAIDS defective
       virus mutant was unable to induce expansion of infected cells and was
       nonpathogenic. These results emphasize the essential role of Pr60gag in
       the disease process. Our data also suggest that Pr60gag, once recruited
       to the cell membrane through its myristylation, interacts with other
       membrane-bound effectors to send signals to induce proliferation of the
       infected cells and to initiate immune dysfunctions.
 DE    Animal  B-Lymphocytes/CYTOLOGY  Base Sequence  Defective Viruses  DNA
       Primers/CHEMISTRY  Gene Products, gag/*METABOLISM  Leukemia Viruses,
       Murine/METABOLISM/*PATHOGENICITY  Lymphocyte Transformation  Mice  Mice,
       Inbred C57BL  Molecular Sequence Data  Murine Acquired Immunodeficiency
       Syndrome/*MICROBIOLOGY  Mutagenesis, Site-Directed
       Myristates/*METABOLISM  Protein Processing, Post-Translational
       Structure-Activity Relationship  Support, Non-U.S. Gov't  JOURNAL
       ARTICLE

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