NLRX1 mediates the disruption of intestinal mucosal function caused by porcine astrovirus infection via the ERK/MLCK pathway

Abstract

Abstract Considering the possible zoonotic nature of Porcine astrovirus (PAstV) and its frequent co-infection with porcine epidemic diarrhoea virus (PEDV), we investigated the impact of NLRX1 on the dysfunction of the intestinal mucosal barrier induced by PAstV infection. The study revealed a significant up-regulation of NLRX1 and LC3 II proteins in Caco-2 cells infected with PAstV. The reduction in PAstV titer occurred with the silencing of NLRX1 and the treatment of the autophagy inhibitor 3-MA. However, the use of 3-MA did not impact the expression of NLRX1. Additionally, PAstV infection triggered the activation of the ERK/MLC pathway and led to the down-regulation of tight junction proteins (Occludin and ZO-1) as well as MUC-2 expression. Silencing the expression of NLRX1 or treating it with 3-MA demonstrated the ability to inhibit MLC phosphorylation and elevate the levels of Occludin and ZO-1 proteins. Moreover, the inhibition of MLC phosphorylation was observed by treating the ERK inhibitor PD98059. Furthermore, adding the MLC inhibitor ML-7 mitigated the down-regulation of mucosa-related protein expression induced by PAstV infection. Nevertheless, the administration of PD98059 and ML-7 did not affect the expression of NLRX1. In summary, the data from this study confirm that NLRX1 plays a role in the disruption of intestinal mucosal function triggered by PAstV infection via the ERK/MLCK pathway. This information contributes to a better understanding of the pathogenesis of PAstV.