RT Journal Article SR Electronic(1) A1 Jacob, Thary A1 Broeke, CĂ©line Van den A1 Waesberghe, Cliff Van A1 Troys, Leen Van A1 Favoreel, Herman W.YR 2015 T1 Pseudorabies virus US3 triggers RhoA phosphorylation to reorganize the actin cytoskeleton JF Journal of General Virology, VO 96 IS 8 SP 2328 OP 2335 DO https://doi.org/10.1099/vir.0.000152 PB Microbiology Society, SN 1465-2099, AB The conserved alphaherpesvirus serine/threonine kinase US3 causes dramatic changes in the actin cytoskeleton, consisting of actin stress fibre breakdown and protrusion formation, associated with increased virus spread. Here, we showed that US3 expression led to RhoA phosphorylation at serine 188 (S188), one of the hallmarks of suppressed RhoA signalling, and that expression of a non-phosphorylatable RhoA variant interfered with the ability of US3 to induce actin rearrangements. Furthermore, inhibition of cellular protein kinase A (PKA) eliminated the ability of US3 to induce S188 RhoA phosphorylation, pointing to a role for PKA in US3-induced RhoA phosphorylation. Hence, the US3 kinase leads to PKA-dependent S188 RhoA phosphorylation, which contributes to US3-mediated actin rearrangements. Our data suggest that US3 efficiently usurps the antagonistic RhoA and Cdc42/Rac1/p21-activated kinase signalling branches to rearrange the actin cytoskeleton., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.000152