Duckling short beak and dwarfism syndrome virus infection activates host innate immune response involving both DNA and RNA sensors

Chen, S. and Fang, T. and Xiao, S. and Lin, F. and Cheng, X. and Wang, S. and Zhu, X. and Chen, X. and Zheng, M. and Munir, M. and Huang, M. and Yu, F. (2020) Duckling short beak and dwarfism syndrome virus infection activates host innate immune response involving both DNA and RNA sensors. Microbial pathogenesis, 138: 103816. ISSN 0882-4010

Abstract

Duckling short beak and dwarfism syndrome virus (SBDSV), a newly identified goose parvovirus, causes devastating disease in domestic waterfowl and considerable economic losses to Chinese waterfowl industry. The molecular pathogenesis of SBDSV infection, nature and dynamics of host immune responses against SBDSV infection remained elusive. In this study, we systematically explored the relative mRNA expression profiles of major innate immune-related genes in SBDSV infected duck embryo fibroblasts. We found that SBDSV infection effectively activated host innate immune responses and resulted in significant up-regulation of IFN-beta and several vital IFN-stimulated genes (ISGs). These up-regulation responses were mainly attributed to viral genomic DNA and dsRNA replication intermediates. Importantly, the expression of cGAS was significantly induced, whereas the expression of other DNA receptors including DDX41, STING, ZBP1, LSM14A and LRRFIP1 have no significant change. Furthermore, SBDSV infection also activates the up-regulation of TLR3 and inhibited the expression of TLR2 and TLR4; however, no effect was observed on the expression of TLR1, TLR5, TLR7, TLR15 and TLR21. Intriguingly, SBDSV infection significantly up-regulated the expression of RNA sensors such as MDA5 and LGP2, and resulted in a delayed but significant up-regulation of RIG-I gene. Taken together, these data indicate that host multiple sensors including DNA sensor (cGAS) and RNA sensors (TLR3, MDA5 and LGP2) are involved in recognizing a variety of different pathogen associated molecular patterns (PAMPs) including viral genomic ssDNA and dsRNA replication intermediates, which trigger an effective antiviral innate immune response.