Human cytomegalovirus mediates cell cycle progression through G1 into early S phase in terminally differentiated cells

Sinclair, John; Baillie, J.; Bryant, Linda A.; Caswell, Richard

doi:10.1099/0022-1317-81-6-1553

Cited by 48 publications

(53 citation statements)

References 67 publications

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“…The up-regulation of E2F-responsive genes indicates cell cycle progression from G 0 ͞G 1 to S phase. Because the viral IE86 protein alone induces cell cycle progression into S phase and cellular DNA synthesis (11,(29)(30)(31) and transactivates the expression of cellular as well as viral genes (14-17, 22, 24), we assayed the effect of the IE86 protein on global cellular gene expression. HFF cells were transduced with recombinant adenovirus vectors expressing either the IE86 protein or GFP, and cytoplasmic RNAs were assayed by DNA microarray.…”

Section: Discussionmentioning

confidence: 99%

“…The IE86 protein alone pushes quiescent, serum-starved cells into S phase, but mutant IE86 protein does not (11,29,30). In IE86 protein expressing cells, cell division does not occur (11,30,31).…”

mentioning

confidence: 99%

“…In IE86 protein expressing cells, cell division does not occur (11,30,31). Because HCMV may require cell cycle progression for replication in terminally differentiated cells, and the IE86 protein alone induces cyclin E expression and cell cycle progression to S phase, we determined the effect of the IE86 protein on global cellular gene expression.…”

mentioning

confidence: 99%

“…Cyclin E and cdks are highly activated after HCMV infection of HFF cells (4,(18)(19)(20). In addition, GST-IE86 fusion protein interacts in vitro with a variety of transcription factors that include histone acetyltransferase, CREB, TBP, TEF-1, TFIIB, and TAFII-130, and cell cycle regulatory factors that include p53, RB, and p21 (11,14,16,(21)(22)(23)(24)(25)(26)(27). The Rb protein has also been reported to bind the IE86 protein in vivo (22,28).…”

mentioning

confidence: 99%

“…The E2F transcription factors activate the promoters for DNA synthesis and G 1 ͞S regulatory genes (10). HCMV infection has been shown to cause hyperphosphorylation of Rb (4,11).…”

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confidence: 99%

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Effect of the human cytomegalovirus IE86 protein on expression of E2F-responsive genes: A DNA microarray analysis

Song

Stinski

2002

Proc. Natl. Acad. Sci. U.S.A.

108

100

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…The E2F transcription factors activate the promoters for DNA synthesis and G 1 ͞S regulatory genes (10). HCMV infection has been shown to cause hyperphosphorylation of Rb (4,11).…”

mentioning

confidence: 99%

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Effect of the human cytomegalovirus IE86 protein on expression of E2F-responsive genes: A DNA microarray analysis

Song

Stinski

2002

Proc. Natl. Acad. Sci. U.S.A.

108

100

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The S phase of the cell cycle and its perturbation by human cytomegalovirus

Bain

2007

Reviews in Medical Virology

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Human cytomegalovirus (HCMV) is a complex human herpesvirus that is known to productively infect a wide range of cell types. In addition, it has been suggested to contribute to some proliferative disorders, particularly atherosclerosis. Consistent with this, a number of studies have shown that HCMV profoundly affects normal cell cycle control. Specifically, the virus can stimulate early entry into S phase thus ensuring adequate resources for viral DNA replication. Importantly, however, the virus concomitantly inhibits potentially competing cellular DNA synthesis allowing cellular precursors to be used for viral but not cellular DNA replication. The mechanisms by which HCMV perturbs S phase entry involve interactions between the virus and the cellular replication machinery such that formation of competent pre-replication complexes (Pre-RC) at cellular origins of replication is restricted in infected cells.

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Regulation of Cellular Genes by Cytomegalovirus

Stinski¹,

Song²

Structure-Function Relationships of Human Pathogenic Viruses

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Cytomegaloviruses (CMVs) are members of the betaherpesviruses with the prototype of this classification group being human CMV. Animal CMVs, such as simian, guinea pig, rat, and murine CMV, have also been used to study betaherpesvirus replication and pathogenesis. Human and animal CMVs have many genes in common. For example, murine CMV, the most widely used model for CMV pathogenesis, has 78 open reading frames (ORFs) in common with the greater than 200 ORFs of human CMV. Two human viruses that are also genetically related to human CMV are human herpesvirus-6 (HHV-6) and HHV-7 which are associated with a disseminated infection in children called roseola.Depending on location and economic status, between 40 and 90% of the population is infected with human CMV. The virus is the leading cause of congenital birth defects which include brain damage and sight and hearing defects. The virus also establishes disseminated infections in immunosuppressed individuals that can result in pneumonitis, retinitis, hepatitis, and gastroenteritis (Alford and Britt, 1990;Ho, 1991). The stromal and epithelial tissues are frequently damaged by CMV infection. In addition, both human and animal CMVs infect vascular endothelial and smooth muscle cells. CMV DNAs are detectable in lesions of the blood vessel (Melnick et al., 1994). A correlation between CMV infection of smooth muscle cells and migration of these cells has been shown, and it is

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Human cytomegalovirus mediates cell cycle progression through G1 into early S phase in terminally differentiated cells

Cited by 48 publications

References 67 publications

Effect of the human cytomegalovirus IE86 protein on expression of E2F-responsive genes: A DNA microarray analysis

Effect of the human cytomegalovirus IE86 protein on expression of E2F-responsive genes: A DNA microarray analysis

The S phase of the cell cycle and its perturbation by human cytomegalovirus

Regulation of Cellular Genes by Cytomegalovirus

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