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Journal of Virology, October 2001, p. 9415-9426, Vol. 75, No. 19
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.19.9415-9426.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
RING Finger Z Protein of Lymphocytic
Choriomeningitis Virus (LCMV) Inhibits Transcription and RNA
Replication of an LCMV S-Segment Minigenome
Tatjana I.
Cornu and
Juan Carlos
de la
Torre*
Division of Virology, Department of
Neuropharmacology, The Scripps Research Institute, La Jolla, California
92037
Received 26 January 2001/Accepted 22 June 2001
Arenaviruses have a bisegmented negative-strand RNA genome whose
proteomic capability is limited to only four polypeptides, namely,
nucleoprotein (NP), surface glycoprotein (GP) that is proteolytically
processed into GP1+GP2, polymerase (L), and a small (11-kDa) RING
finger protein (Z). The role of Z during the Lymphocytic
choriomeningitis virus (LCMV) life cycle is poorly understood.
We investigated the function of Z in virus transcription and
replication by using a reverse genetic system for the prototypic arenavirus LCMV. This system involves an LCMV minigenome and the minimal viral trans-acting factors (NP and L), expressed
from separated cotransfected plasmids. Cotransfection of the Z cDNA strongly inhibited LCMV minigenome expression. The effect required synthesis of Z protein; its magnitude was dose dependent and occurred with levels of Z protein substantially lower than those observed in
LCMV-infected cells. Coexpression of Z did not prevent the encapsidation of plasmid supplied minigenome, but it affected both
transcription and RNA replication similarly. Mutations in Z that
unfolded its RING finger domain eliminated its inhibitory activity, but
RING proteins not related to Z did not affect LCMV minigenome
expression. Consistent with the minigenome results, cells transiently
expressing Z exhibited decreased susceptibility to infection with LCMV.
*
Corresponding author. Mailing address: The Scripps
Research Institute, Department of Neuropharmacology, IMM-6, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9462. Fax: (858) 784-9981. E-mail: juanct{at}scripps.edu.

Publication 13869-NP from The Scripps Research
Institute.
Journal of Virology, October 2001, p. 9415-9426, Vol. 75, No. 19
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.19.9415-9426.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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