Document Detail


Correlation between interferon sensitivity of reovirus isolates and ability to discriminate between normal and Ras-transformed cells.
MedLine Citation:
PMID:  15831962     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mammalian reoviruses exhibit a propensity to replicate in transformed cells. It is currently believed that the interferon-inducible RNA-dependent protein kinase (PKR), an intracellular host-cell resistance factor that is inhibited by an activated Ras-dependent pathway in transformed cells, is responsible for this discrimination. In the present study, reovirus isolates differing in their sensitivity to interferon were obtained by chemical mutagenesis, and examined for their replicative properties in parental and Ras-transformed mouse NIH-3T3 cells. It was observed that most isolates can bypass resistance mechanisms of parental cells at high m.o.i., and that there is a correlation between the ability to discriminate between transformed and parental cells, and interferon sensitivity. Most interestingly, an interferon-hypersensitive mutant virus was more dependent on Ras activation than any other viral isolate. Altogether, this suggests that optimal reovirus isolates could be selected to attack tumour cells depending on the nature of the alterations in interferon-inducible pathways found in these cells.
Authors:
Penny Rudd; Guy Lemay
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of general virology     Volume:  86     ISSN:  0022-1317     ISO Abbreviation:  J. Gen. Virol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-15     Completed Date:  2005-05-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1489-97     Citation Subset:  IM    
Affiliation:
Département de Microbiologie et Immunologie, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada H3C 3J7.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiviral Agents / pharmacology*
Cell Transformation, Neoplastic*
Cells, Cultured
Interferons / pharmacology*
Mice
Microbial Sensitivity Tests
Mutagenesis
Orthoreovirus, Mammalian / drug effects*,  genetics,  physiology*
Chemical
Reg. No./Substance:
0/Antiviral Agents; 9008-11-1/Interferons

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