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Inhibition of viral replication by ribozyme: mutational analysis of the site and mechanism of antiviral activity.


ABSTRACT: A controlled mutational study was used to determine the site and mechanism of the antiviral action of ribozymes that inhibit Sindbis virus replication. A hairpin ribozyme targeting G575 of the Sindbis virus genomic RNA was designed and cloned into a minimized alphavirus amplicon vector. Cells that were stably transfected with this construct expressed low levels of a constitutive transcript containing the ribozyme plus recognition sequences for Sindbis RNA replicase. Upon infection, the ribozyme transcript was amplified to high levels by the viral replicase, resulting in decreased viral production from infected ribozyme-expressing cells. Mutations were then introduced into the viral RNA target sequence to interfere with ribozyme binding, and compensatory changes were generated in the ribozy

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC1075678 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature