PUBLICATION

Fish female-biased gene cyp19a1a leads to female antiviral response attenuation between sexes by autophagic degradation of MITA

Authors

Lu, L.F., Jiang, J.Y., Du, W.X., Wang, X.L., Li, Z.C., Zhou, X.Y., Zhang, C., Mou, C.Y., Chen, D.D., Li, Z., Zhou, L., Gui, J.F., Li, X.Y., Li, S.

ID

ZDB-PUB-220622-68

Date

2022

Source

PLoS pathogens 18: e1010626 (Journal)

Registered Authors

Gui, Jian-Fang, Li, Zhi, Zhou, Li

Keywords

none

MeSH Terms

Herpesviridae*
Zebrafish/genetics
Mammals
Fish Diseases*
Autophagy
Carps*
Female
Antiviral Agents/pharmacology
Immunity, Innate/genetics
Animals
Male

(all 11)

PubMed

35727817 Full text @ PLoS Pathog.

Abstract

From insects to mammals, both innate and adaptive immune response are usually higher in females than in males, with the sex chromosome and hormonal differences considered the main reasons. Here, we report that zebrafish cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a), an autosomal gene with female-biased expression, causes female fish to exhibit a lower antiviral response. First, we successfully constructed an infection model by intraperitoneal injection of spring viremia of carp virus (SVCV) into zebrafish (Danio rerio) and Carassius auratus herpesvirus (CaHV) in gibel carp (Carassius gibelio). Specifically, female fish were more vulnerable to viral infection than males, accompanied by a significantly weaker interferon (IFN) expression. After screening several candidates, cyp19a1a, which was highly expressed in female fish tissues, was selected for further analysis. The IFN expression and antiviral response were significantly higher in cyp19a1a-/- than in cyp19a1a+/+. Further investigation of the molecular mechanism revealed that Cyp19a1a targets mediator of IRF3 activation (MITA) for autophagic degradation. Interestingly, in the absence of MITA, Cyp19a1a alone could not elicit an autophagic response. Furthermore, the autophagy factor ATG14 (autophagy-related 14) was found interacted with Cyp19a1a to either promote or attenuate Cyp19a1a-mediated MITA degradation by either being overexpressed or knocked down, respectively. At the cellular level, both the normal and MITA-enhanced cellular antiviral responses were diminished by Cyp19a1a. These findings demonstrated a sex difference in the antiviral response based on a regulation mechanism controlled by a female-biased gene besides sex chromosome and hormonal differences, supplying the current understanding of sex differences in fish.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	female organism gonad dysplastic, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	female organism heart dysplastic, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	female organism spleen dysplastic, abnormal	Fig. 2
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	female organism spleen dysplastic, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	female organism viability, abnormal	Fig. 2
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	female organism viability, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	female organism viral transcription increased rate, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	gonad dysplastic, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	heart dysplastic, abnormal	Fig. 1
AB	viral treatment by injection: Sprivivirus cyprinus	Days 45-89 to Adult	male organism spleen dysplastic, abnormal	Fig. 2

1 - 10 of 24

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ihb158		Small Deletion	cyp19a1a

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
AB
cyp19a1a^{ihb158/ihb158}

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-myc	monoclonal		IgG1	Mouse
Ab7-map1lc3b	polyclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Mapping

Lu et al., 2022 ZDB-PUB-220622-68 PMID:35727817

Fish female-biased gene cyp19a1a leads to female antiviral response attenuation between sexes by autophagic degradation of MITA

Lu et al., 2022

ZDB-PUB-220622-68
PMID:35727817