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M9490420.TXT
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1994-09-19
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).