RESUMO
Orf virus (ORFV) infects sheep and goat tissues, resulting in severe proliferative lesions. To analyze cellular protein expression in ORFV-infected goat skin fibroblast (GSF) cells, we used two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ). The proteomics approach was used along with quantitative reverse transcription polymerase chain reaction (RT-qPCR) to detect differentially expressed proteins in ORFV-infected GSF cells and mock-infected GSF cells. A total of 282 differentially expressed proteins were identified. It was found that 222 host proteins were upregulated and 60 were downregulated following viral infection. We confirmed that these proteins were differentially expressed and found that heat shock 70-kDa protein 1B (HSPA1B) was differentially expressed and localized in the cytoplasm. It was also noted that HSPA1B caused inhibition of viral proliferation, in the middle and late stages of viral infection. The differentially expressed proteins were associated with the biological processes of viral binding, cell structure, signal transduction, cell adhesion, and cell proliferation.
Assuntos
Fibroblastos/metabolismo , Proteínas de Choque Térmico HSP70/fisiologia , Vírus do Orf/fisiologia , Proteoma/genética , Replicação Viral , Animais , Células Cultivadas , Cromatografia Líquida , Fibroblastos/virologia , Cabras , Interações Hospedeiro-Patógeno , Vírus do Orf/genética , Proteômica , Espectrometria de Massas em TandemRESUMO
As a zoonotic disease, ovine contagious pustular dermatitis (Orf) is a serious threat to sheep as well as humans. Orf virus (ORFV) interferon resistance protein (VIR) is the principal virulence protein that encodes a dsRNA-binding protein to inhibit host antiviral response. p53 is one of the key proteins of the host antiviral innate immunity. It not only enhances type I interferon secretion but also induces apoptosis in infected cells, and plays a crucial role in the immune response against various viral infections. However, it remains to be elucidated what role p53 plays in ORFV replication and whether ORFV's own protein VIR regulates p53 expression to promote self-replication. In this study, we showed that p53 has an antiviral effect on ORFV and can inhibit ORFV replication. In addition, ORFV nonstructural protein VIR interacts with p53 and degrades p53, which inhibits p53-mediated positive regulation of downstream antiviral genes. This study provides new insight into the immune evasion mediated by ORFV and identifies VIR as an antagonistic factor for ORFV to evade the antiviral response.
Assuntos
Interações entre Hospedeiro e Microrganismos/genética , Vírus do Orf/genética , Proteína Supressora de Tumor p53/genética , Proteínas Virais/genética , Replicação Viral/genética , Animais , Linhagem Celular , Cricetinae , Ectima Contagioso/virologia , Fibroblastos/imunologia , Fibroblastos/virologia , Regulação Viral da Expressão Gênica , Cabras , Evasão da Resposta Imune/genética , Imunidade Inata , Rim/citologia , Vírus do Orf/fisiologia , Ovinos , Pele/citologia , Proteínas Virais/metabolismoRESUMO
Tumor progression locus 2 (TPL2) is a serine/threonine kinase that belongs to the MAP3K family. The activated TPL2 regulates the innate immune-relevant signaling pathways, such as ERK, JNK, and NF-κB, and the differentiation of immune cells, for example, CD4+ T and NK cells. Therefore, TPL2 plays a critical role in regulating the innate immune response. The present review summarizes the recent advancements in the TPL2-regulated innate immune response.
