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The interplay between Araçatuba virus and host signaling pathways: role of PI3K/Akt in viral replication

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Abstract

In this study, we describe the interaction between Araçatuba virus (ARAV), a naturally occurring Brazilian vaccinia virus isolated from an outbreak at a dairy farm, and the host cell’s signal transduction pathways. Even though ARAV infection led to phosphorylation of MAPKs MEK/ERK, JNK, and p38MAPK, genetic or pharmacological inhibition of these pathways had no impact on viral replication. We also provide evidence that ARAV stimulated the phosphorylation of Akt (PKB) at serine 473 (S473-P), a signaling event that is required for full activation of Akt during the infectious cycle. Furthermore, pharmacological inhibition of PI3K (LY294002) abrogated ARAV-induced Akt activation (S473-P) and affected early and late viral gene expression, which was followed by a decrease in virus yield (~1 log). Taken together, our data shed some light onto the biological differences between ARAV and vaccinia virus strain WR (VACV-WR), which could contribute, at least in part, to the low-virulence phenotype displayed by ARAV. Thus, while the requirement for the PI3K/Akt pathway for successful ARAV replication is also shared with VACV-WR and cowpox virus strain BR (CPXV-BR), ARAV showed a lower replicative capacity, as well as a smaller plaque-size phenotype after infection of A31 cells when compared to VACV-WR.

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Acknowledgments

We are grateful to Angela S. Lopes, Ilda M. V. Gama, João R. dos Santos, and Andreza A. Carvalho for their secretarial and technical assistance. We also thank Dr. Bruno S.A.F. Brasil for critical reading of the manuscript. We are grateful to Dr. M. C. Sogayar (Department of Biochemistry, University of São Paulo, Brazil), who kindly provided us with the A31 cell line, and Dr. R. Davis (Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA) for the WT and JNK1/2 double KO cells. WT and egr-1 KO cells were kindly provided by Dr. E. Adamson (The Burnham Institute, Torrey Pines Road, La Jolla, CA, USA). The rabbit polyclonal antibodies against viral proteins CrmA/SPI-2 were a gift from Dr. D. Pickup (Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA), and A17, D8, F18 and H3 were from Dr. B. Moss (NIAID, Bethesda, MD, USA). The rabbit polyclonal antibody against the viral A3 protein was from Dr. P. Traktman (Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA). This work was supported by Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazilian Ministry of Culture, Science, and Technology, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). MHAF was a recipient and LCO is recipient of a pre-doctoral fellowship from CNPq. FLBM is recipient of an undergraduate fellowship from CNPq (PIBIC). CAB, EGK, GST and PCPF are recipients of research fellowships from CNPq.

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Authors and Affiliations

  1. Grupo de Transdução de Sinal/Orthopoxviruses, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Marcelo H. A. de Freitas, Leonardo C. de Oliveira, Fernanda L. B. Mügge & Cláudio A. Bonjardim

  2. Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, Belo Horizonte, MG, 31270-901, Brazil

    Marcelo H. A. de Freitas, Leonardo C. de Oliveira, Fernanda L. B. Mügge, Paulo C. P. Ferreira, Giliane de S. Trindade, Erna G. Kroon & Cláudio A. Bonjardim

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  1. Marcelo H. A. de Freitas
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Correspondence to Cláudio A. Bonjardim.

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de Freitas, M.H.A., de Oliveira, L.C., Mügge, F.L.B. et al. The interplay between Araçatuba virus and host signaling pathways: role of PI3K/Akt in viral replication. Arch Virol 156, 1775–1785 (2011). https://doi.org/10.1007/s00705-011-1052-6

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