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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shahi, S. Shanmugasundaram, G. K. Banerjea, A. C. |
| Description | Author Affiliation: Shahi S ( Laboratory of Virology, National Institute of Immunology, New Delhi-110067, India.); |
| Abstract | Reovirus genome segment S1 encodes protein final sigma1, which is the receptor binding protein, modulates tissue tropism, and specifies the nature of the antiviral immune response. It makes up less than 2% of reovirus particles and is synthesized in very small amounts in infected cells. Any antiviral strategy aimed at reducing specifically the expression of this genome segment should, in principle, reduce the infectivity of the virus. To test this hypothesis, we have assembled two hammer-head motif-containing ribozymes (Rzs) targeted to cleave at the conserved B and C domains of the reovirus s1 RNA. Protein-independent but Mg(2+)-dependent sequence-specific cleavage of s1 RNA was achieved by both the Rzs in trans. Cells that transiently express these Rzs, when challenged with reovirus, were protected against the cytopathic effects caused by the virus. This protection correlated with the specific intracellular reduction of s1 transcripts that was due to their cleavage by the Rzs. Rz-treated cells that were challenged with reovirus showed almost complete disappearance of protein final sigma1 without significantly altering the levels of the other reovirus structural proteins. Thus, Rzs, besides acting as antiviral agents, could be exploited as biological tools to delineate specific functions of target genes. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 98 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2001-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | RNA, Catalytic Metabolism RNA, Viral Animals Blotting, Western COS Cells Gene Expression Regulation, Viral Drug Effects Genome, Viral HeLa Cells Kinetics Magnesium Chloride Pharmacology Orthoreovirus Genetics Physiology Therapeutic Use Reoviridae Infections Prevention & Control Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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