A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization.
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.
Grupo de Transdução de Sinal/Orthopoxvirologiaa and Laboratório de Vírus,Universidade Federal de Minas Gerais, Minas Gerais, Belo Horizonte, Brazil.
Anna C T C
AC
Pereira
Flávia G G
FG
Leite
Bruno S A F
BS
Brasil
Jamaria A P
JA
Soares-Martins
Alice A
AA
Torres
Paulo F P
PF
Pimenta
Thaïs
T
Souto-Padrón
Paula
P
Traktman
Paulo C P
PC
Ferreira
Erna G
EG
Kroon
Cláudio A
CA
Bonjardim
D000818:Animals; D002465:Cell Movement; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D048688:MAP Kinase Kinase 7 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014615:Vaccinia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology*
D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482570:Map2k7 protein, mouse