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

Höti, Naseruddin; Johnson, Tamara Jane; Chowdhury, Wasim H.; Rodriguez, Ronald

doi:10.3390/cancers10060202

Open AccessArticle

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

by

Naseruddin Höti

^1,†,

Tamara Jane Johnson

^2,†,

Wasim H. Chowdhury

³

and

Ronald Rodriguez

^3,*

¹

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA

²

James Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA

³

Department of Urology, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to the work.

Cancers 2018, 10(6), 202; https://doi.org/10.3390/cancers10060202

Submission received: 10 May 2018 / Revised: 6 June 2018 / Accepted: 11 June 2018 / Published: 15 June 2018

(This article belongs to the Special Issue Oncolytic Virotherapy)

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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.

Keywords: adenovirus replication; p21; oncolytic adenovirus

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MDPI and ACS Style

Höti, N.; Johnson, T.J.; Chowdhury, W.H.; Rodriguez, R. Loss of Cyclin-Dependent Kinase Inhibitor Alters Oncolytic Adenovirus Replication and Promotes More Efficient Virus Production. Cancers 2018, 10, 202. https://doi.org/10.3390/cancers10060202

AMA Style

Höti N, Johnson TJ, Chowdhury WH, Rodriguez R. Loss of Cyclin-Dependent Kinase Inhibitor Alters Oncolytic Adenovirus Replication and Promotes More Efficient Virus Production. Cancers. 2018; 10(6):202. https://doi.org/10.3390/cancers10060202

Chicago/Turabian Style

Höti, Naseruddin, Tamara Jane Johnson, Wasim H. Chowdhury, and Ronald Rodriguez. 2018. "Loss of Cyclin-Dependent Kinase Inhibitor Alters Oncolytic Adenovirus Replication and Promotes More Efficient Virus Production" Cancers 10, no. 6: 202. https://doi.org/10.3390/cancers10060202

APA Style

Höti, N., Johnson, T. J., Chowdhury, W. H., & Rodriguez, R. (2018). Loss of Cyclin-Dependent Kinase Inhibitor Alters Oncolytic Adenovirus Replication and Promotes More Efficient Virus Production. Cancers, 10(6), 202. https://doi.org/10.3390/cancers10060202

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

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