Abstract
Newcastle disease (ND), an acute and highly contagious avian disease caused by virulent Newcastle disease virus (NDV), often results in severe economic losses worldwide every year. Although it is clear that microRNAs (miRNAs) are implicated in modulating innate immune response to invading microbial pathogens, their role in host defense against NDV infection remains largely unknown. Our prior study indicates that gga-miR-19b-3p is up-regulated in NDV-infected DF-1 cells (a chicken embryo fibroblast cell line) and functions to suppress NDV replication. Here we report that overexpression of gga-miR-19b-3p promoted the production of NDV-induced inflammatory cytokines and suppressed NDV replication, whereas inhibition of endogenous gga-miR-19b-3p expression had an opposite effect. Dual-luciferase and gene expression array analyses revealed that gga-miR-19b-3p directly targets the mRNAs of ring finger protein 11 (RNF11) and zinc-finger protein, MYND-type containing 11 (ZMYND11), two negative regulators of nuclear factor kappa B (NF-κB) signaling, in DF-1 cells. RNF11 and ZMYND11 silencing by small interfering RNA (siRNA) induced NF-κB activity and inflammatory cytokine production, and suppressed NDV replication; whereas ectopic expression of these two proteins exhibited an opposite effect. Our study provides evidence that gga-miR-19b-3p activates NF-κB signaling by targeting RNF11 and ZMYND11, and that enhanced inflammatory cytokine production is likely responsible for the suppression of NDV replication.
Highlights
Newcastle disease virus (NDV) was first described in the early 1900s as the contagious agent of the fatal avian disease known as chicken pest (Dimitrov et al, 2016, 2017)
For miRNA transfection, DF-1 cells were transfected with gga-miR-19b-3p mimic and inhibitor and mimic negative control and inhibitor negative control at a final concentration of 100 nM using EL Transfection Reagent (Transgen Biotech, China) following the manufacturer’s instructions
We first conducted qRT-polymerase chain reaction (PCR) to determine if NDV infection regulated gga-miR-19b-3p expression in DF-1 cells
Summary
Newcastle disease virus (NDV) was first described in the early 1900s as the contagious agent of the fatal avian disease known as chicken pest (Dimitrov et al, 2016, 2017). It is classified as an avian paramyxovirus-1 (APMV-1) in the Avulavirus genus of the family Paramyxoviridae (Cheng et al, 2016). Due to the wide range of host and high genetic diversity, the failure of Newcastle disease (ND) vaccine immunization and reduction of vaccine efficiency often occur in cultivation industry worldwide (Miller et al, 2009, 2013)
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