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J. Biol. Chem., Vol. 277, Issue 36, 33099-33104, September 6, 2002
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From the Institut für Virologie der
Philipps-Universität Marburg, Robert-Koch-Strasse 17, Marburg
35037, Germany
Transcription of the highly pathogenic Ebola
virus (EBOV) is dependent on VP30, a constituent of the viral
nucleocapsid complex. Here we present evidence that phosphorylation of
VP30, which takes place at six N-terminal serine residues and one
threonine residue, is of functional significance. Replacement of the
phosphoserines by alanines resulted in an only slightly phosphorylated
VP30 (VP306A) that is still able to activate
EBOV-specific transcription in a plasmid-based minigenome system.
VP306A, however, did not bind to inclusions that are
induced by the major nucleocapsid protein NP. Three intracellular
phosphatases (PP1, PP2A, and PP2C) have been determined to
dephosphorylate VP30. The presence of okadaic acid (OA), an inhibitor
of PP1 and PP2A, had the same negative effect on transcription
activation by VP30 as the substitution of the six phosphoserines for
aspartate residues. OA, however, did not impair transcription when VP30
was replaced by VP306A. In EBOV-infected cells, OA blocked
virus growth dose-dependently. The block was mediated by
the extensive phosphorylation of VP30, which is evidenced by the result
that expression of VP306A, in trans, led to the
progression of EBOV infection in the presence of OA. In conclusion,
phosphorylation of VP30 was shown to regulate negatively transcription
activation and positively binding to the NP inclusions.
Phosphorylation of VP30 Impairs Ebola Virus Transcription*
*
The work was supported by the Deutsche
Forschungsgemeinschaft (Sonderforschungsbereich 286, TP A6,
Sonderforschungsbereich 535, TP A9) and the Fazit Stiftung (to J. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Tel.: 64-21-286-5433;
Fax: 64-21-286-5482; E-mail: becker@mailer.uni-marburg.de.
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