Abstract
BackgroundHuman T-cell leukemia virus type I (HTLV-I) has efficiently adapted to its host and establishes a persistent infection characterized by low levels of viral gene expression and slow proliferation of HTLV-I infected cells over decades. We have previously found that HTLV-I p30 is a negative regulator of virus expression.ResultsIn this study we show that p30 targets multiple cell cycle checkpoints resulting in a delayed entry into S phase. We found that p30 binds to cyclin E and CDK2 and prevents the formation of active cyclin E-CDK2 complexes. In turn, this decreases the phosphorylation levels of Rb and prevents the release of E2F and its transcriptional activation of genes required for G1/S transition. Our studies also show that HTLV-II p28 does not bind cyclin E and does not affect cell cycle progression.ConclusionsIn contrast to HTLV-I, the HTLV-II-related retrovirus is not oncogenic in humans. Here we report that the HTLV-I p30 delays cell cycle progression while its homologue, HTLV-II p28, does not, providing evidence for important differences between these two related retrovirus proteins.
Highlights
Human T-cell leukemia virus type I (HTLV-I) has efficiently adapted to its host and establishes a persistent infection characterized by low levels of viral gene expression and slow proliferation of HTLV-I infected cells over decades
We show that the effect of p30 is due to its interaction with the cyclin E key-trigger of the G1/S transition, which in turn reduces the function of the Cyclin E-CDK2 complex and all the downstream events
To facilitate analyses of p30 expressing cells by FACS, p30 was cloned into a vector containing an internal ribosome entry site (IRES) fused to the green fluorescent protein (GFP)
Summary
Human T-cell leukemia virus type I (HTLV-I) has efficiently adapted to its host and establishes a persistent infection characterized by low levels of viral gene expression and slow proliferation of HTLV-I infected cells over decades. Cell cycle progression from G1 to S phase is regulated by the sequential activation of two kinase-complexes, CDK4/6-cyclin D and Cyclin E-CDK2 [1], to ease the inhibition of E2F-mediated transcription. Cyclin E-Cdk phosphorylates Rb on different sites from the cyclin D-dependent kinases, and may differentially affect interactions of Rb with E2Fs, histone deacetylases, and other chromatin-remodeling factors [9]. Cyclin E-Cdk phosphorylates a second set of substrates that are involved in cell duplication; these events affect histone gene expression, centrosome duplication, replication origin licensing, and, possibly, origin firing [10]. Once the E2F transcriptional program is initiated and sufficient levels of cyclin E-dependent Cdk activity is attained, cells no longer rely on the cyclin D-dependent kinases nor on persistent mitogenic signals and are committed to complete the cell cycle [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
