Loss-of-function MAVS mutation causes antiviral immunodeficiency:unveiling a novel mechanism linking viral infection to generalized pustular psoriasis in children
10.16016/j.2097-0927.202509092
- VernacularTitle:MAVS功能丧失性突变导致抗病毒免疫缺陷:揭示病毒感染触发儿童泛发性脓疱性银屑病的新机制
- Author:
Yanan SUN
1
;
Jiahong ZHOU
;
Yaqin LIU
;
Juan YANG
;
Shasha MENG
;
Hongmei LI
;
Weihui ZHOU
Author Information
1. 重庆医科大学附属儿童医院儿科研究所
- Keywords:
psoriasis;
mitochondrial antiviral signaling protein;
infections;
inflammation
- From:
Journal of Army Medical University
2025;47(23):2953-2962
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of mitochondrial antiviral signaling protein(MAVS)in viral infection-triggered generalized pustular psoriasis(GPP)in children.Methods This retrospective case-control study enrolled 80 GPP patients aged 0～18 years from Children's Hospital of Chongqing Medical University(from October 2013 to April 2019).Whole-exome sequencing identified rare MAVS variants associated with GPP.Pathogenicity of variants was predicted using Mutation Taster,Disease Association,SIFT,and CADD bioinformatics tools.Sanger sequencing validated variants,followed by construction of wild-type(WT)and mutant MAVS expression plasmids transfected into HEK 293 cells.Protein expression was assessed by Western blot.Dual-luciferase reporter gene assays measured IFNB1 and NF-κB transcriptional activity.Genotype distribution of the MAVS c.171dupT/p.H57fs variant was analyzed using Fisher's exact test.Results This study enrolled 80 pediatric GPP patients(aged 0～18 years).Whole-exome sequencing identified five rare MAVS variants,with bioinformatics analyses predicting deleterious effects on protein stability and function.Western blot demonstrated that the c.171dupT mutation in GPP patients significantly reduced full-length MAVS expression(P<0.001);dual-luciferase assays further revealed this variant impaired MAVS-mediated IFNB1 transcriptional activation by 85%(P<0.001),abrogated NF-κB signaling pathway activation(P<0.001),but exhibited no dominant-negative effect on wild-type MAVS function(P>0.05).Conclusion The MAVS c.171dupT frameshift variant may contribute to infection-triggered GPP in children,suggesting its potential as a genetic biomarker for GPP susceptibility.
