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In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellular translational apparatus. While transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cellular translational control pathways in enabling the latent-lytic switch have not been described. Using PEL-derived B-cells naturally infected with KSHV as a model, we define efficient reactivation conditions and demonstrate that reactivation substantially changes the protein synthesis profile. New polypeptide synthesis correlates with 4E-BP1 translational repressor inactivation, nuclear PABP accumulation, eIF4F assembly, and phosphorylation of the capbinding protein eIF4E by Mnk1. Significantly, inhibiting Mnk1 reduces accumulation of the critical viral transactivator RTA through a post-transcriptional mechanism, limiting downstream lytic protein production, and impairs reactivation efficiency. Thus, herpesvirus reactivation from latency activates the host cap-dependent translation machinery, illustrating the importance of translational regulation in implementing new developmental instructions that drastically alter cell fate. [ABSTRACT FROM AUTHOR]

The stimuli-triggered cell attachment/detachment from responsive polymer-coated surfaces is influenced by several parameters including electrostatic interactions, wettability and swelling of the polymer coating. Herein, the supported dual thermo- and pH-responsive cationic poly(N-isopropylacrylamide) microgel, surface-functionalized with polyethylene glycol (PEG) or poly-2-dimethylaminoethylmethacrylate (PDMAEMA), were used as substrates to investigate the role of these parameters on the cell behavior. The microgel were covalently immobilized on glass coverslips and their stimuli-triggered cell detachment ability towards cultured bEnd.3, MCF7 and U138 cell lineages was investigated. The microgel surface-functionalized with PEG chains presented cell adhesion and proliferation rates comparable to controls, while providing the best thermo-triggered detachment performance with MCF7 and U138 cells. This behavior was associated with a preserved hydrophilic character of the microgel surface regardless of the temperature and pH. The swelling behavior of all microgels tuned by pH gave rise to significant cellular detachment only for U138 cells. However, bEnd.3 cell detachment could not be triggered neither by temperature nor pH, regardless of the microgel surface coating. [Display omitted] • Responsive microgel coatings modulate the attachment/detachment behavior of cells. • Cell attachment and proliferation on microgel coatings is similar to the controls. • Triggered cell detachment is favored on microgels surface-functionalized with PEG. • Detachment could not be triggered by any responsive microgel for bEnd.3 cells. [ABSTRACT FROM AUTHOR]