Erschienen in:
15.06.2017 | Original Article
c-Jun integrates signals from both MEK/ERK and MKK/JNK pathways upon vaccinia virus infection
verfasst von:
Flávia G. G. Leite, Alice A. Torres, Leonardo C. De Oliveira, André F. P. Da Cruz, Jamária A. P. Soares-Martins, Anna C. T. C. Pereira, Giliane S. Trindade, Jonatas S. Abrahão, Erna G. Kroon, Paulo C. P. Ferreira, Cláudio A. Bonjardim
Erschienen in:
Archives of Virology
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Ausgabe 10/2017
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Abstract
Usurpation of the host’s signalling pathways is a common strategy employed by viruses to promote their successful replication. Here we show that infection with the orthopoxvirus vaccinia virus (VACV) leads to sustained stimulation of c-Jun activity during the entire infective cycle. This stimulation is temporally regulated through MEK/ERK or MKK/JNK pathways, i.e. during the early/mid phase (1 to 6 hpi) and in the late phase (9 to 24 hpi) of the infective cycle, respectively. As a transcriptional regulator, upon infection with VACV, c-Jun is translocated from the cytoplasm to the nucleus, where it binds to the AP-1 DNA sequence found at the promoter region of its target genes. To investigate the role played by c-Jun during VACV replication cycle, we generated cell lines that stably express a c-Jun-dominant negative (DNc-Jun) mutation. Our data revealed that c-Jun is required during early infection to assist with viral DNA replication, as demonstrated by the decreased amount of viral DNA found in the DNc-Jun cells. We also demonstrated that c-Jun regulates the expression of the early growth response gene (egr-1), a gene previously shown to affect VACV replication mediated by MEK/ERK signalling. VACV-induced stimulation of the MKK/JNK/JUN pathway impacts viral dissemination, as we observed a significant reduction in both viral yield, during late stages of infection, and virus plaque size. Collectively, our data suggest that, by modulating the host’s signalling pathways through a common target such as c-Jun, VACV temporally regulates its infective cycle in order to successfully replicate and subsequently spread.