Phosphorylation of Shrimp Tcf by a Viral Protein Kinase WSV083 Suppresses Its Antiviral Effect.

Chuanqi Wang,Lingwei Ruan,Hong Shi,Sujie Li,Linmin Liu,Wenyang Lin

doi:10.3389/fimmu.2021.698697

Abstract

Nuclear DNA-binding TCF proteins, which act as the main downstream effectors of Wnt signaling, are essential for the regulation of cell fate and innate immunity. However, their role during viral infection in shrimp remains unknown. Herein, we demonstrated that Litopenaeus vannamei TCF (LvTcf) acts independently of Lvβ-catenin to promote interferon-like protein LvVago1 production, thus mounting the response to WSSV infection. Further, we observed that WSV083, a WSSV serine/threonine protein kinase, bound to LvTcf and phosphorylated it. Phosphorylated LvTcf was then recognized and degraded via the ubiquitin-proteasome pathway. Moreover, mass spectrometry analyses indicated that the T39 and T104 residues of LvTcf were target sites phosphorylated by WSV083. Point mutation analyses suggested that additional sites of LvTcf may undergo phosphorylation via WSV083. Taken together, the current work provides valuable insights into host immunity and viral pathogenesis. LvTcf is not only a modulator of shrimp innate immunity but is also an important target for WSSV immune evasion. Thus, the current findings will help improve disease control in shrimps.

Highlights

White spot syndrome virus (WSSV) is the only species within the Whispovirus genus of the Nimaviridae family [1,2,3]
We found that shrimp TCF, referred to as Litopenaeus vannamei TCF (LvTcf), plays a protective role against WSSV infection by promoting the production of shrimp interferon-like protein LvVago1 in an Lvbcatenin-independent manner
Multiple sequence alignment suggested that the LvTcf highmobility group (HMG) domain had several highly-conserved Ser/Thr/ Lys phosphorylation sites (Figure S1C)

Summary

Introduction

White spot syndrome virus (WSSV) is the only species within the Whispovirus genus of the Nimaviridae family [1,2,3] It is a large double-stranded circular DNA virus with a genome of approximately 300 kb containing 181 open reading frames (ORFs). Shrimp mount humoral and cellular immune responses [7] to defend against viral infection These rely on several key cell signaling cascades, including the Toll/IMD-NF-kB and JAK/ STAT pathways, among others, which transduce extracellular signals into cells and promote the expression of antimicrobial peptides or other immune effector molecules to combat WSSV infection [8,9,10]. WSSV employs a number of mechanisms to ensure propagation To this end, the virus hijacks host proteins to facilitate gene transcription.

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Results

Conclusion