Selection of genetic inhibitors of rabies virus

Selection of genetic inhibitors of rabies virus A cDNA library of short random fragments derived from four of the five genes of the rabies virus genome has been used to isolate genetic suppressor elements (GSEs) expressed intracellularly that inhibit rabies virus replication. Two nucleotide fragments, one from the rabies virus nucleocapsid protein (N) gene and the other from the phosphoprotein (P) gene, have been identified as inhibitors of rabies virus replication in cell culture. The N cDNA fragment is expressed in sense-orientation and could produce a dominant negative protein affecting virus replication. The P cDNA fragment is expressed in the inhibitory antisense direction. Inhibition of rabies virus replication was detected in cell culture using an ELISA for detection of rabies virus glycoprotein expression on the cell surface and immunofluorescence for detection of intracellular rabies virus N expression. Both the sense and antisense GSEs, because of their targeted inhibition of rabies virus replication, have possible uses in rational design of antiviral compounds for treatment of rabies. This approach could be applied to any virus, particularly to those that lyse their target host cell. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Selection of genetic inhibitors of rabies virus

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Publisher
Springer-Verlag
Copyright
Copyright © 2004 by Springer-Verlag/Wien
Subject
LifeSciences
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-004-0299-6
Publisher site
See Article on Publisher Site

Abstract

A cDNA library of short random fragments derived from four of the five genes of the rabies virus genome has been used to isolate genetic suppressor elements (GSEs) expressed intracellularly that inhibit rabies virus replication. Two nucleotide fragments, one from the rabies virus nucleocapsid protein (N) gene and the other from the phosphoprotein (P) gene, have been identified as inhibitors of rabies virus replication in cell culture. The N cDNA fragment is expressed in sense-orientation and could produce a dominant negative protein affecting virus replication. The P cDNA fragment is expressed in the inhibitory antisense direction. Inhibition of rabies virus replication was detected in cell culture using an ELISA for detection of rabies virus glycoprotein expression on the cell surface and immunofluorescence for detection of intracellular rabies virus N expression. Both the sense and antisense GSEs, because of their targeted inhibition of rabies virus replication, have possible uses in rational design of antiviral compounds for treatment of rabies. This approach could be applied to any virus, particularly to those that lyse their target host cell.

Journal

Archives of VirologySpringer Journals

Published: Aug 1, 2004

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