Human cytomegalovirus IE86 protein binds to cellular Mcm3 protein but does not inhibit its binding to the Epstein-Barr virus oriP in U373MG-p220.2 cells

Ye, Song; Mf, Stinski

doi:10.4149/av_2010_02_125

Cited by 2 publications

(3 citation statements)

References 17 publications

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“…We then tested whether IE86 also interacted with MCM3AP. Figure 3A clearly shows that, whilst IE86 appeared to bind weakly to MCM3 (lane 11), consistent with previous observations [25], a strong interaction was observed between IE86 and MCM3AP in vitro (lane 9). As before, we observed the relevant presence or absence of binding of IE86 to positive and negative controls (IE86 and gelsolin, tracks 8 and 7 respectively).…”

Section: Resultssupporting

confidence: 90%

“…The targeting of cell cycle by HCMV is crucial for efficient lytic infection and HCMV encodes multiple factors which positively and negatively regulate host DNA replication: this likely ensures an optimum environment for viral DNA replication [6], [12], [18], [21], [23], [25]. IE72, IE86, pp71, and pUL97, when individually over-expressed, are known to inactivate pRb-family proteins resulting in the activation of E2F-dependent S-phase gene expression, which promotes a G1/S-transition.…”

Section: Discussionmentioning

confidence: 99%

“…However, little is known about the mechanisms by which other viral factors, such as pUL69 [24] and IE86 [12], [25], inhibit cellular DNA synthesis.…”

Section: Introductionmentioning

confidence: 99%

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The Cellular Protein MCM3AP Is Required for Inhibition of Cellular DNA Synthesis by the IE86 Protein of Human Cytomegalovirus

et al. 2012

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Like all DNA viruses, human cytomegalovirus (HCMV) infection is known to result in profound effects on host cell cycle. Infection of fibroblasts with HCMV is known to induce an advance in cell cycle through the G0-G1 phase and then a subsequent arrest of cell cycle in early S-phase, presumably resulting in a cellular environment optimum for high levels of viral DNA replication whilst precluding replication of cellular DNA. Although the exact mechanisms used to arrest cell cycle by HCMV are unclear, they likely involve a number of viral gene products and evidence points to the ability of the virus to prevent licensing of cellular DNA synthesis. One viral protein known to profoundly alter cell cycle is the viral immediate early 86 (IE86) protein - an established function of which is to initially drive cells into early S phase but then inhibit cellular DNA synthesis. Here we show that, although IE86 interacts with the cellular licensing factor Cdt1, it does not inhibit licensing of cellular origins. Instead, IE86-mediated inhibition of cellular DNA synthesis requires mini-chromosome-maintenance 3 (MCM3) associated protein (MCM3AP), which can cause subsequent inhibition of initiation of cellular DNA synthesis in a licensing-independent manner.

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Section: Resultssupporting

confidence: 90%