Abstract:
:Mouse hepatitis virus strain A59 (MHV-A59) encodes within the 22-kb gene 1 a large polyprotein containing three proteinase domains with proven or predicted cysteine catalytic residues. E64d, a specific, irreversible inhibitor of cysteine (thiol) proteinases, inhibits the processing of the gene 1 polyprotein. Specifically, E64d blocks the carboxy-terminal cleavage of p65. E64d also inhibits replication of MHV-A59 in murine DBT cells in a dose-dependent manner, resulting in reduced virus titers and viral syncytia formation. This inhibition of replication is associated with a rapid shutoff of new viral RNA synthesis, in a manner similar to that seen in the presence of cycloheximide. The E64d-associated inhibition of RNA synthesis likely results from E64d-specific inhibition of processing of the gene 1 polyprotein, resulting in inactive proteinase or replicase proteins. These results indicate that processing of the MHV-A59 gene 1-encoded polyprotein is required throughout infection to sustain RNA synthesis and virus replication.
journal_name
Virologyjournal_title
Virologyauthors
Kim JC,Spence RA,Currier PF,Lu X,Denison MRdoi
10.1006/viro.1995.1123subject
Has Abstractpub_date
1995-04-01 00:00:00pages
1-8issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(85)71123-3journal_volume
208pub_type
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