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• W2169797594 abstract "ABSTRACT Viral fusogenic membrane proteins have been proposed as tools to increase the potency of oncolytic viruses, but there is a need for mechanisms to control the spread of fusogenic viruses in normal versus tumor cells. We have previously shown that a mutant of the paramyxovirus simian virus 5 (SV5) that harbors mutations in the P/V gene from the canine parainfluenza virus (P/V-CPI − ) is a potent inducer of type I interferon (IFN) and apoptosis and is restricted for spread through normal but not tumor cells in vitro. Here, we have used the cytopathic P/V-CPI − as a backbone vector to test the hypothesis that a virus expressing a hyperfusogenic glycoprotein will be a more effective oncolytic vector but will retain sensitivity to IFN. A P/V mutant virus expressing an F protein with a glycine-to-alanine substitution in the fusion peptide (P/V-CPI − -G3A) was more fusogenic than the parental P/V-CPI − mutant. In two model prostate tumor cell lines which are defective in IFN production (LNCaP and DU145), the hyperfusogenic P/V-CPI − -G3A mutant had normal growth properties at low multiplicities of infection and was more effective than the parental P/V-CPI − mutant at cell killing in vitro. However, in PC3 cells which produce and respond to IFN, the hyperfusogenic P/V-CPI − -G3A mutant was attenuated for growth and spread. Killing of PC3 cells was equivalent between the parental P/V-CPI − mutant and the hyperfusogenic P/V-CPI − -G3A mutant. In a nude mouse model using LNCaP cells, the hyperfusogenic P/V-CPI − -G3A mutant was more effective than P/V-CPI − at reducing tumor burden. In the case of DU145 tumors, the two vectors based on P/V-CPI − were equally effective at limiting tumor growth. Together, our results provide proof of principle that a cytopathic SV5 P/V mutant can serve as an oncolytic virus and that the oncolytic effectiveness of P/V mutants can be enhanced by a fusogenic membrane protein without compromising sensitivity to IFN. The potential advantages of SV5-based oncolytic vectors are discussed." @default.
• W2169797594 created "2016-06-24" @default.
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• W2169797594 date "2008-10-01" @default.
• W2169797594 modified "2023-10-18" @default.
• W2169797594 title "A Hyperfusogenic F Protein Enhances the Oncolytic Potency of a Paramyxovirus Simian Virus 5 P/V Mutant without Compromising Sensitivity to Type I Interferon" @default.
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• W2169797594 doi "https://doi.org/10.1128/jvi.01054-08" @default.
• W2169797594 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2546974" @default.
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