Article (Scientific journals)
Rho-ROCK and Rac-PAK Signaling Pathways Have Opposing Effects on the Cell-to-Cell Spread of Marek’s Disease Virus
Richerioux, Nicolas; Blondeau, Caroline; Wiedemann, Agnes et al.
2012In PLoS ONE
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Keywords :
Marek's disease virus; cell-to-cell spread; actin cytoskeleton; Rho/Rac signaling pathways
Abstract :
[en] Marek’s Disease Virus (MDV) is an avian alpha-herpesvirus that only spreads from cell-to-cell in cell culture. While its cell-tocell spread has been shown to be dependent on actin filament dynamics, the mechanisms regulating this spread remain largely unknown. Using a recombinant BAC20 virus expressing an EGFPVP22 tegument protein, we found that the actin cytoskeleton arrangements and cell-cell contacts differ in the center and periphery of MDV infection plaques, with cells in the latter areas showing stress fibers and rare cellular projections. Using specific inhibitors and activators, we determined that Rho-ROCK pathway, known to regulate stress fiber formation, and Rac-PAK, known to promote lamellipodia formation and destabilize stress fibers, had strong contrasting effects on MDV cell-to-cell spread in primary chicken embryo skin cells (CESCs). Inhibition of Rho and its ROCKs effectors led to reduced plaque sizes whereas inhibition of Rac or its group I-PAKs effectors had the adverse effect. Importantly, we observed that the shape of MDV plaques is related to the semi-ordered arrangement of the elongated cells, at the monolayer level in the vicinity of the plaques. Inhibition of Rho-ROCK signaling also resulted in a perturbation of the cell arrangement and a rounding of plaques. These opposing effects of Rho and Rac pathways in MDV cell-to-cell spread were validated for two parental MDV recombinant viruses with different ex vivo spread efficiencies. Finally, we demonstrated that Rho/Rac pathways have opposing effects on the accumulation of N-cadherin at cell-cell contact regions between CESCs, and defined these contacts as adherens junctions. Considering the importance of adherens junctions in HSV-1 cell-to-cell spread in some cell types, this result makes of adherens junctions maintenance one potential and attractive hypothesis to explain the Rho/Rac effects on MDV cell-to-cell spread. Our study provides the first evidence that MDV cell-to-cell spread is regulated by Rho/Rac signaling.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Richerioux, Nicolas ;  Institut Scientifique de Recherche Agronomique - INRA > Sante Animale > UMR1282, Infectious Diseases and Public Health, ISP, BIOVA team, Tours-Nouzilly
Blondeau, Caroline  ;  University College London - UCL > Infection and Immunity > Medical Research Council Centre for Medical Molecular Virology
Wiedemann, Agnes ;  Institut Scientifique de Recherche Agronomique - INRA > Sante Animale > UMR1282, Infectious Diseases and Public Health, ISP, SPVB team, Tours-Nouzilly
Remy, Sylvie;  Institut Scientifique de Recherche Agronomique - INRA > Sante Animale > UMR1282, Infectious Diseases and Public Health, ISP, BIOVA team, Tours-Nouzilly
Vautherot, Jean-Francois;  Institut Scientifique de Recherche Agronomique - INRA > Sante Animale > UMR1282, Infectious Diseases and Public Health, ISP, BIOVA team, Tours-Nouzilly
Denesvre, Caroline;  Institut Scientifique de Recherche Agronomique - INRA > Sante Animale > UMR1282, Infectious Diseases and Public Health, ISP, BIOVA team, Tours-Nouzilly
 These authors have contributed equally to this work.
Language :
English
Title :
Rho-ROCK and Rac-PAK Signaling Pathways Have Opposing Effects on the Cell-to-Cell Spread of Marek’s Disease Virus
Publication date :
2012
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 13 March 2015

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