PUBLICATION

LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response

Authors: Gong, X.Y., Zhang, Q.M., Zhao, X., Li, Y.L., Qu, Z.L., Li, Z., Dan, C., Gui, J.F., Zhang, Y.B.
ID: ZDB-PUB-220820-6
Date: 2022
Source: iScience 25: 104821 (Journal)
Registered Authors: Gui, Jian-Fang, Li, Zhi, Zhang, Yi-Bing
Keywords: Biochemistry, Immunology, Virology
MeSH Terms: none
PubMed: 35982787 Full text @ iScience

Abstract

In mammals, LGP2 is the enigmatic RLR family member, being initially believed as an inhibitor of RLR-triggered IFN response but subsequently as an activator of MDA5 signaling and an inhibitor of RIG-I signaling. The contradiction happens to fish LGP2. Here, we generate a lgp2 loss-of-function (lgp2^lof/lof ) zebrafish mutant, which is highly susceptible to SVCV infection, displaying an initially decreased activation of IFN response and a following increased one. Mechanistically, zebrafish LGP2 functions as the essential activator of IFN response dependent on MDA5 at the early stage of viral infection but as a negative regulator by impairing mRNA levels of tbk1 and ikki at the late stage of viral infection. The function switch of LGP2 is related to cellular IFN production during viral infection. Our data demonstrate that zebrafish LGP2 is a key homeostatic regulator of IFN response and thus essential for zebrafish survival against SVCV infection.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89	gill	RTPCR	Fig. 1
AB	standard conditions	Adult	gill	WB	Fig. 1
AB	standard conditions	Days 45-89	gill	RTPCR	Fig. 1
AB	standard conditions	Days 45-89	head kidney	RTPCR	Fig. 1
AB	standard conditions	Days 45-89	liver	RTPCR	Fig. 1
AB	standard conditions	Days 45-89	posterior kidney	RTPCR	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89	posterior kidney	RTPCR	Fig. 1
AB	standard conditions	Days 45-89	spleen	RTPCR	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	standard conditions	Days 45-89	gill	RTPCR	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	standard conditions	Adult	gill	WB	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	viral treatment by exposure to environment: Sprivivirus cyprinus	Day 6	whole organism viability, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89	gill dhx58 expression increased amount, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89	posterior kidney dhx58 expression increased amount, abnormal	Fig. 1
dhx58^ihbybz001/+ (AB)	standard conditions	Adult	gill dhx58 expression decreased amount, abnormal	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	standard conditions	Days 45-89	gill dhx58 expression decreased amount, abnormal	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	standard conditions	Days 45-89	head kidney dhx58 expression decreased amount, abnormal	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	standard conditions	Days 45-89	liver dhx58 expression decreased amount, abnormal	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	standard conditions	Days 45-89	spleen dhx58 expression decreased amount, abnormal	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	standard conditions	Adult	gill dhx58 expression decreased amount, abnormal	Fig. 1
dhx58^{ihbybz001/ihbybz001} (AB)	viral treatment by exposure to environment: Sprivivirus cyprinus	Day 6	viral genome replication increased occurrence, abnormal	Fig. 1

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ihbybz001		Indel	dhx58

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
dhx58	TALEN1-dhx58	TALEN

Fish

Fish
AB
dhx58^{ihbybz001/ihbybz001} (AB)
dhx58^ihbybz001/+ (AB)

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Gong et al., 2022 ZDB-PUB-220820-6 PMID:35982787

LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response

Gong et al., 2022

ZDB-PUB-220820-6
PMID:35982787