Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication

Wade A. Bresnahan; Istvan Boldogh; Ping Chi; E. Aubrey Thompson; Thomas Albrecht

doi:10.1006/viro.1997.8489

Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication

Wade A. Bresnahan, Istvan Boldogh, Ping Chi, E. Aubrey Thompson, Thomas Albrecht

Cancer Biology

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132 Scopus citations

Abstract

Human cytomegalovirus is a herpesvirus that induces numerous cellular processes upon infection. Among these are activation of cyclin-dependent kinase 2, which regulates cell cycle progression in G1 and S phase. We report here that inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2 activity by roscovitine inhibits HCMV DNA synthesis, production of infectious progeny, and late antigen expression in infected cells in a dose-dependent manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant negative mutant, whereas expression of wild- type Cdk2 has no effect on viral replication. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication.

Original language	English (US)
Pages (from-to)	239-247
Number of pages	9
Journal	Virology
Volume	231
Issue number	2
DOIs	https://doi.org/10.1006/viro.1997.8489
State	Published - May 12 1997

ASJC Scopus subject areas

Virology

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10.1006/viro.1997.8489

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@article{9f0424217dc34aee8f2128718975ce68,

title = "Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication",

abstract = "Human cytomegalovirus is a herpesvirus that induces numerous cellular processes upon infection. Among these are activation of cyclin-dependent kinase 2, which regulates cell cycle progression in G1 and S phase. We report here that inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2 activity by roscovitine inhibits HCMV DNA synthesis, production of infectious progeny, and late antigen expression in infected cells in a dose-dependent manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant negative mutant, whereas expression of wild- type Cdk2 has no effect on viral replication. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication.",

author = "Bresnahan, {Wade A.} and Istvan Boldogh and Ping Chi and Thompson, {E. Aubrey} and Thomas Albrecht",

note = "Funding Information: We thank Dr. Laurent Meijer for supplying the roscovitine and communicating results prior to publication; Dr. Ed Harlow for the pCMVCdk2-wt-HA and pCMVCdk2-dn-HA expression vectors; and Dr. Wade Gibson for supplying the UL80.5 antibody. A special thanks to Drs. J. Wade Harper and Tien Ko for critically reading the manuscript. This work was supported by NIH Grant DE11389 and EPA Grant R81-9394 to T.B.A. and by NIH Grants AG10514 and CA24347 to E.A.T., and by NIH Grant ES06676. W.A.B. is a James W. McLaughlin Predoctoral Fellow.",

year = "1997",

month = may,

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doi = "10.1006/viro.1997.8489",

language = "English (US)",

volume = "231",

pages = "239--247",

journal = "Virology",

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AU - Bresnahan, Wade A.

AU - Boldogh, Istvan

AU - Chi, Ping

AU - Thompson, E. Aubrey

AU - Albrecht, Thomas

N1 - Funding Information: We thank Dr. Laurent Meijer for supplying the roscovitine and communicating results prior to publication; Dr. Ed Harlow for the pCMVCdk2-wt-HA and pCMVCdk2-dn-HA expression vectors; and Dr. Wade Gibson for supplying the UL80.5 antibody. A special thanks to Drs. J. Wade Harper and Tien Ko for critically reading the manuscript. This work was supported by NIH Grant DE11389 and EPA Grant R81-9394 to T.B.A. and by NIH Grants AG10514 and CA24347 to E.A.T., and by NIH Grant ES06676. W.A.B. is a James W. McLaughlin Predoctoral Fellow.

PY - 1997/5/12

Y1 - 1997/5/12

N2 - Human cytomegalovirus is a herpesvirus that induces numerous cellular processes upon infection. Among these are activation of cyclin-dependent kinase 2, which regulates cell cycle progression in G1 and S phase. We report here that inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2 activity by roscovitine inhibits HCMV DNA synthesis, production of infectious progeny, and late antigen expression in infected cells in a dose-dependent manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant negative mutant, whereas expression of wild- type Cdk2 has no effect on viral replication. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication.

AB - Human cytomegalovirus is a herpesvirus that induces numerous cellular processes upon infection. Among these are activation of cyclin-dependent kinase 2, which regulates cell cycle progression in G1 and S phase. We report here that inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2 activity by roscovitine inhibits HCMV DNA synthesis, production of infectious progeny, and late antigen expression in infected cells in a dose-dependent manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant negative mutant, whereas expression of wild- type Cdk2 has no effect on viral replication. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication.

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JF - Virology

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ER -

Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication

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