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Journal of Virology, April 2000, p. 3293-3300, Vol. 74, No. 7
Department of Biochemistry, Dalhousie
University, Halifax, Nova Scotia, Canada B3H
4H71; Department of Physiology and
Biophysics, Mt. Sinai School of Medicine, New York, New York
100292; and Department of Pathology
and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin
53706-15323
Received 26 July 1999/Accepted 30 December 1999
Only a few host cell proteins that associate with arenaviruses have
been identified. To date, the arenavirus Z protein associates with the
promyelocytic leukemia protein PML and the ribosomal P proteins. The
majority of PML is present in nuclear bodies which are translocated to
the cytoplasm by infection with the arenavirus, lymphocytic
choriomeningitis virus (LCMV). The Z protein is a small zinc-binding
RING protein with an unknown function which is required for the viral
life cycle. Here, we demonstrate an association between Z and the host
cell translation factor, eukaryotic initiation factor 4E (eIF-4E) in
infected and transfected cells. Z's association with both ribosomal
proteins and this translation factor led us to investigate whether Z
could modulate host cell translation. In cell culture, Z selectively
represses protein production in an eIF-4E-dependent manner.
Specifically, we see reduction in cyclin D1 protein production with no
effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cells
transfected with Z. Previous reports indicate that cyclin D1 is
sensitive to eIF-4E levels, whereas GAPDH is not. Consistent with this,
we observe preferential downregulation of cyclin D1 during infection
and no effect on GAPDH. Further, no changes in RNA levels were observed
for cyclin D1 or GAPDH transcripts. The interaction between eIF-4E and
Z may provide a mechanism for slower growth observed in infected cells
and a viral strategy for establishing chronic infection.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The Lymphocytic Choriomeningitis Virus RING Protein
Z Associates with Eukaryotic Initiation Factor 4E and Selectively
Represses Translation in a RING-Dependent Manner
*
Corresponding author. Mailing address: Department of
Physiology and Biophysics, Mt. Sinai School of Medicine, One Gustave Levy Pl., New York, NY 10029-6574. Phone: (212) 659-8677. Fax: (212)
849-2456. E-mail: kathyb{at}inka.mssm.edu.
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