Abstract
The function of Toll pathway defense against bacterial infection has been well established in shrimp, however how this pathway responds to viral infection is still largely unknown. In this study, we report the Toll4-Dorsal-AMPs cascade restricts the white spot syndrome virus (WSSV) infection of shrimp. A total of nine Tolls from Litopenaeus vannamei namely Toll1-9 are identified, and RNAi screening in vivo reveals the Toll4 is important for shrimp to oppose WSSV infection. Knockdown of Toll4 results in elevated viral loads and renders shrimp more susceptible to WSSV. Furthermore, Toll4 could be a one of upstream pattern recognition receptor (PRR) to detect WSSV, and thereby leading to nuclear translocation and phosphorylation of Dorsal, the known NF-κB transcription factor of the canonical Toll pathway. More importantly, silencing of Toll4 and Dorsal contributes to impaired expression of a specific set of antimicrobial peptides (AMPs) such as anti-LPS-factor (ALF) and lysozyme (LYZ) family, which exert potent anti-WSSV activity. Two AMPs of ALF1 and LYZ1 as representatives are demonstrated to have the ability to interact with several WSSV structural proteins to inhibit viral infection. Taken together, we therefore identify that the Toll4-Dorsal pathway mediates strong resistance to WSSV infection by inducing some specific AMPs.
Highlights
Multicellular organisms have evolved for the ability to protect themselves from a wide variety of pathogens such as viruses
The Toll-like receptors (TLRs) pathway mediated antiviral immune response is well identified in mammals, yet, Toll pathway governing this protection in invertebrates remains unknown
The innate immune response is generally initiated via the detection of pathogen-associated molecular patterns (PAMPs), some evolutionarily conserved structures or motifs shared by broad classes of invading organisms, by a wide diversity of host pattern recognition receptors (PRRs) [1]
Summary
Multicellular organisms have evolved for the ability to protect themselves from a wide variety of pathogens such as viruses. In invertebrates including shrimps that lacking immunoglobulin-based adaptive immune system, this protection is provided through the action of an innate immune system. The innate immune response is generally initiated via the detection of pathogen-associated molecular patterns (PAMPs), some evolutionarily conserved structures or motifs shared by broad classes of invading organisms, by a wide diversity of host pattern recognition receptors (PRRs) [1]. Mammalian TLRs play universal and pivotal roles in host defenses mainly via the innate immune system, and the immunoglobulin-based adaptive immune system that are devoid in invertebrate [3]. The function of TLR signaling pathway is clearly clarified, and the ten TLRs can directly recognize and bind to a number of diverse molecular structures, including lipids (e.g., TLR4: LPS via MD2; TLR1/2/6: lipoproteins), proteins (e.g., TLR5: flagellin; TLR2 and TLR4: HMGB1), and nucleic acids (e.g., TLR3: dsRNA; TLR7/8: ssRNA; and TLR9: unmethylated CpG motifs in bacterial, viral, and fungal DNA) [4]. The stimulation of TLRs results in activation of the NF-κB (nuclear factor κB) transcription factors that drive the transcription of proinflammatory cytokines, or/ and trigger IRF (interferon regulatory factor) transcription factors that induce transcription of type I interferon cytokines, both of which confer immune response against infection [2, 4]
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