Loss of Cyclin-Dependent Kinase Inhibitor Alters Oncolytic Adenovirus Replication and Promotes More Efficient Virus Production

细胞周期蛋白依赖性激酶抑制剂的缺失会改变溶瘤腺病毒的复制并促进更高效的病毒生产

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作者:Naseruddin Höti, Tamara Jane Johnson, Wasim H Chowdhury, Ronald Rodriguez

Abstract

We elucidate the role of p21/Waf-1, a cyclin-dependent kinase inhibitor, on the oncolytic infection and replication cycle of adenovirus by studying both mRNA and adenoviral proteins expression. We found that infection in the absence of p21 causes a significant increase in adenoviral genomes and late gene expression. Similarly, the oncolytic adenoviral infected p21−/− cells have earlier formation of replication foci and robust replication kinetics that were not observed in the wild type p21/Waf-1 intact cells. These findings suggest a culmination that the presence of intact p21 in host cells causes defects in the oncolytic viral life cycle which results in the production of immature and noninfectious particles.

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