Progressive Accumulation of Activated ERK2 within Highly Stable ORF45-Containing Nuclear Complexes Promotes Lytic Gammaherpesvirus Infection

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In this study, we find that lytic RRV infection leads to selective and progressive accumulation of pERK2 within RRV ORF45 (R45)-containing nuclear complexes in infected cells. In these complexes, pERK2 decays with first order kinetics and a half-life of nearly 3 hours, suggesting a highly stable complex with a slow R45 off-rate, while pERK1 decays with a half-life of less than 30 minutes, consistent with its accessibility to cellular phosphatases. We further describe that despite the apparent sequestration of pERK2 within the R45 complexes, downstream activation of pERK nuclear substrates remains robust, promoting virion production. Using confocal microscopy and FRET analyses, we show that R45 closely interacts with both pERK2 and pRSK2 in the nucleus in heterodimeric or heterotrimeric complexes. Lastly, although we demonstrate that RSK ectopic overexpression augments the levels of pERK2 in 293 cells co-transfected with R45, its role in ERK2 activation and virion production during RRV infection is not essential, in apparent contrast to its requirement during KSHV infection.

Vyšlo v časopise: Progressive Accumulation of Activated ERK2 within Highly Stable ORF45-Containing Nuclear Complexes Promotes Lytic Gammaherpesvirus Infection. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004066
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004066

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