Faculty Collaboration Database

A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization. J Virol 2012 Jan;86(1):172-84

Date

10/28/2011

Pubmed ID

22031940

Pubmed Central ID

PMC3255887

DOI

10.1128/JVI.05638-11

Scopus ID

2-s2.0-84855953854 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

Viral manipulation of transduction pathways associated with key cellular functions such as survival, response to microbial infection, and cytoskeleton reorganization can provide the supportive milieu for a productive infection. Here, we demonstrate that vaccinia virus (VACV) infection leads to activation of the stress-activated protein kinase (SAPK)/extracellular signal-regulated kinase (ERK) 4/7 (MKK4/7)-c-Jun N-terminal protein kinase 1/2 (JNK1/2) pathway; further, the stimulation of this pathway requires postpenetration, prereplicative events in the viral replication cycle. Although the formation of intracellular mature virus (IMV) was not affected in MKK4/7- or JNK1/2-knockout (KO) cells, we did note an accentuated deregulation of microtubule and actin network organization in infected JNK1/2-KO cells. This was followed by deregulated viral trafficking to the periphery and enhanced enveloped particle release. Furthermore, VACV infection induced alterations in the cell contractility and morphology, and cell migration was reduced in the JNK-KO cells. In addition, phosphorylation of proteins implicated with early cell contractility and cell migration, such as microtubule-associated protein 1B and paxillin, respectively, was not detected in the VACV-infected KO cells. In sum, our findings uncover a regulatory role played by the MKK4/7-JNK1/2 pathway in cytoskeleton reorganization during VACV infection.

Author List

Pereira AC, Leite FG, Brasil BS, Soares-Martins JA, Torres AA, Pimenta PF, Souto-Padrón T, Traktman P, Ferreira PC, Kroon EG, Bonjardim CA

MESH terms used to index this publication - Major topics in bold

Animals
Cell Movement
Cytoskeleton
Humans
MAP Kinase Kinase 4
MAP Kinase Kinase 7
MAP Kinase Signaling System
Mice
Mice, Inbred BALB C
Mice, Knockout
Mitogen-Activated Protein Kinase 8
Mitogen-Activated Protein Kinase 9
Phosphorylation
Vaccinia
Vaccinia virus