A expressão de interleucina-6 durante infecção pelo Orthopoxvirus Cowpox é regulada pelas MAPKs JNK1/2

• Ano de defesa: 2012
• Autor(a) principal: Alice Abreu Torres
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Microbiologia
• Link de acesso: http://hdl.handle.net/1843/BUBD-A58FHZ

The Orthopoxviruses Vaccinia (VACV) and Cowpox (CPXV) belong to the Poxviridae family, the largest and more complex animal DNA viruses, whose replication occurs in the cytoplasmic compartment of the infected cells. Even though Orthopoxvirus genus is the most studied, little is known about Orthopoxvirus Cowpox (CPXV)-host cell interactions. As virus-host cell interaction plays a decisive role in viral biology, the Grupo de Transdução de Sinal of the Laboratório de Vírus (ICB-UFMG) have been studying the activation of mitogen-activated protein kinases (MAPKs) in response to Orthopoxviruses infections. Previously, we demonstrated that these Orthopoxviruses activates the protein kinases ERK and JNK leading to the phosphorylation of the transcription factor c-Jun, a common substract on both signaling pathways. However, JNK 1/2 was not required for proper VACV and CPXV replication, although they are important in VACV dissemination. Since it has been shown that production of cytokine is regulated by JNK 1/2 during the infection with diverse viruses, we sought to investigate the expression of pro-inflammatory cytokines upon VACV and CPXV infection. By means of quantitative reverse transcription-PCR and ELISA, we demonstrated that CPXV infection of wild-type (WT) or JNK 1/2 knock-out (KO) mouse embryonic fibroblasts (MEFs) leads to a higher induction and secretion of IL-6 cytokine than VACV infection. We also showed a significant increase in IL-6 mRNA expression in KO cells when compared to WT MEFs, mainly at 12 hpi. This result was also confirmed with murine macrophages, by using the JNK inhibitor VIII. We also demonstrated an increase in IL-6 mRNA expression in cells infected with CPXV and expressing dominant-negative c-Jun mutation (DNc-Jun), when compared to infected control cells. Preliminary results also showed that JNK1/2 inhibition results in a reduction of the transcriptional expression of TNF- in MEFs as well as in murine macrophages. Taken together, our data suggest that the JNK/c-Jun pathway exerts a negative regulation of IL-6 mRNA expression upon CPXV infection, leading, thus, to a better understanding of the complex relationship between virus and their host cells.