title: The interplay between Araçatuba virus and host signaling pathways: role of PI3K/Akt in viral replication.
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.
authors: Grupo de Transdução de Sinal/Orthopoxviruses, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Marcelo H A
authors: MH
authors: de Freitas
authors: Leonardo C
authors: LC
authors: de Oliveira
authors: Fernanda L B
authors: FL
authors: Mügge
authors: Paulo C P
authors: PC
authors: Ferreira
authors: Giliane de S
authors: Gde S
authors: Trindade
authors: Erna G
authors: EG
authors: Kroon
authors: Cláudio A
authors: CA
authors: Bonjardim
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000201:enzymology* / Q000821:virology; D002460:Cell Line; D054884:Host-Pathogen Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014615:Vaccinia / Q000201:enzymology / Q000662:veterinary* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt