Upregulation of matrix metalloproteinase (MMP)-14, a major driven force of extracellular-matrix (ECM) remodelling and cell migration, correlates with ECM breakdown and pathologic manifestation of genotype VII Newcastle disease virus (NDV) in chickens. However, the functional relevance between MMP-14 and pathogenesis of genotype VII NDV remains to be investigated. In this study, expression, biofunction and regulation of MMP-14 induced by genotype VII NDV were analysed in chicken peripheral blood mononuclear cells (PBMCs). The results showed that JS5/05 significantly increased expression and membrane accumulation of MMP-14 in PBMCs, correlating to enhanced collagen degradation and cell migration. Specific MMP-14 ... More
Upregulation of matrix metalloproteinase (MMP)-14, a major driven force of extracellular-matrix (ECM) remodelling and cell migration, correlates with ECM breakdown and pathologic manifestation of genotype VII Newcastle disease virus (NDV) in chickens. However, the functional relevance between MMP-14 and pathogenesis of genotype VII NDV remains to be investigated. In this study, expression, biofunction and regulation of MMP-14 induced by genotype VII NDV were analysed in chicken peripheral blood mononuclear cells (PBMCs). The results showed that JS5/05 significantly increased expression and membrane accumulation of MMP-14 in PBMCs, correlating to enhanced collagen degradation and cell migration. Specific MMP-14 inhibition significantly impaired collagen degradation and migration of JS5/05-infected cells, suggesting dependence of these features on MMP-14. In addition, MMP-14 upregulation correlated with activation of the extracellular signal-regulated kinase (ERK) pathway upon JS5/05 infection, and blockage of the ERK signalling significantly suppressed MMP-14-mediated collagen degradation and migration of JS5/05-infected cells. Using a panel of chimeric NDVs derived from gene exchange between genotype VII and IV NDV, the fusion and haemagglutinin-neuraminidase genes were identified as the major viral determinants for MMP-14 expression and activity. In conclusion, MMP-14 was defined as a critical regulator of collagen degradation and cell migration of chicken PBMCs infected with genotype VII NDV, which may contribute to pathology of the virus. Our findings add novel information to the body of knowledge regarding virus-host biology and NDV pathogenesis.
