The vaccinia virus-stimulated mitogen-activated protein kinase (MAPK) pathway is required for virus multiplication

Biochemical Journal - Tập 381 Số 2 - Trang 437-446 - 2004
Anderson Assunção Andrade1,2, Patrícia N. G. Silva1,2, Anna Carolina Toledo da Cunha Pereira1,2, Lirlândia P. Sousa1,2, Paulo César Peregrino Ferreira2, Ricardo T. Gazzinelli3,4, Erna Geessien Kroon2, Catherine Ropert3, Cláudio Antônio Bonjardim1,2
1Grupo de Transdução de Sinal, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, Minas Gerais, Brazil
2Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, Minas Gerais, Brazil
3Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, 31270-901 Belo Horizonte, Minas Gerais, Brazil
4Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, Minas Gerais, Brazil

Tóm tắt

Early events play a decisive role in virus multiplication. We have shown previously that activation of MAPK/ERK1/2 (mitogen-activated protein kinase/extracellular-signal-regulated kinase 1/2) and protein kinase A are pivotal for vaccinia virus (VV) multiplication [de Magalhães, Andrade, Silva, Sousa, Ropert, Ferreira, Kroon, Gazzinelli and Bonjardim (2001) J. Biol. Chem. 276, 38353–38360]. In the present study, we show that VV infection provoked a sustained activation of both ERK1/2 and RSK2 (ribosomal S6 kinase 2). Our results also provide evidence that this pattern of kinase activation depends on virus multiplication and ongoing protein synthesis and is maintained independently of virus DNA synthesis. It is noteworthy that the VGF (VV growth factor), although involved, is not essential for prolonged ERK1/2 activation. Furthermore, our findings suggest that the VV-stimulated ERK1/2 activation also seems to require actin dynamics, microtubule polymerization and tyrosine kinase phosphorylation. The VV-stimulated pathway MEK/ERK1/2/RSK2 (where MEK stands for MAPK/ERK kinase) leads to phosphorylation of the ternary complex factor Elk-1 and expression of the early growth response (egr-1) gene, which kinetically paralleled the kinase activation. The recruitment of this pathway is biologically relevant, since its disruption caused a profound effect on viral thymidine kinase gene expression, viral DNA replication and VV multiplication. This pattern of sustained kinase activation after VV infection is unique. In addition, by connecting upstream signals generated at the cytoskeleton and by tyrosine kinase, the MEK/ERK1/2/RSK2 cascade seems to play a decisive role not only at early stages of the infection, i.e. post-penetration, but is also crucial to define the fate of virus progeny.

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