Key Points

A homolog of the AhR family named LvAhR was cloned and identified from L. vannamei.

Caspases are novel target genes of LvAhR.

The AhR–caspase axis restrains virus replication by promoting antiviral apoptosis.

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates immune modulation following exposure of animals to many environmental xenobiotics. However, its role in innate immune responses during viral infection is not fully understood, especially in invertebrates. In this study, a cDNA encoding an AhR homolog was cloned from an arthropod Litopenaeus vannamei (LvAhR). The expression of LvAhR was strongly upregulated in response to the challenge of white spot syndrome virus, a pathogen of highly contagious and fatal infectious disease of shrimp. The relevance of LvAhR to host defense was underlined by heightened susceptibility and elevated virus loads after AhR-silenced shrimp exposure to white spot syndrome virus. LvAhR could induce an apoptosis response through regulating the expression of L. vannamei caspase-1 (homologous to human caspase-3) by directly targeting its promoter that was required to couple with AhR nuclear translocator. Additionally, knockdown of L. vannamei caspase-1 resulted in elevated virus titers and a lower cell apoptotic rate. Thus, we demonstrate that an AhR–caspase axis restrains virus replication by promoting antiviral apoptosis, supporting a previously unidentified direct link between AhR signaling and caspase-mediated apoptosis signaling and, furthermore, suggests that the AhR–caspase axis could be a potential therapeutic target for enhancing antiviral responses in arthropods.

Footnotes

This work was supported by National Natural Science Foundation of China Grant 32022085/31930113, National Key Research and Development Program of China Grant 2018YFD0900600/2018YFD0900500, Independent Research and Development Projects of Maoming Laboratory Grant 2021ZZ007/2021TDQD004, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) Grant SML2021SP301, Key-Area Research and Development Program of Guangdong Province Grant 2018B020204001, and by Fundamental Research Funds for the Central Universities, Sun Yat-sen University Grant 22lglj05. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The online version of this article contains supplemental material.

C.L., J.H., and Q.F. conceived and designed the experiments; Q.F., H.L., S.W., S.C., X.L., B.X., and C.L. performed the experiments and analyzed data; Q.F., J.H., and C.L. wrote the draft manuscript; C.L. and J.H. acquired funding; X.J. and R.C. provided experimental animals (shrimp); and C.L. was responsible for forming the hypothesis, project development, data coordination, and writing, finalizing, and submitting the manuscript. All authors discussed the results and approved the final version of the manuscript.

Abbreviations used in this article:

AhRaryl hydrocarbon receptorARNTAhR nuclear translocatorbHLHbasic helix-loop-helixDmDcp-1D. melanogaster Dcp-1DmGrimD. melanogaster GrimDmReaperD. melanogaster ReaperFSCforward scatterHAhemagglutininLvAhRL. vannamei AhRLvARNTL. vannamei ARNTLvCaspaseL. vannamei caspaseORFopen reading framePASPer–Arnt–SimPIpropidium iodideqRT-PCRquantitative RT-PCRRACErapid amplification of cDNA endsRNAiRNA interferenceSSCside scatterTADtranscriptional activation domainWSSwhite spot syndromeWSSVWSS virusXRExenobiotic response elementReceived January 10, 2022.Accepted August 24, 2022.Copyright © 2022 by The American Association of Immunologists, Inc.