Domain in Fiber-2 interacted with KPNA3/4 significantly affects the replication and pathogenicity of the highly pathogenic FAdV-4. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Xie, Quan; Wang, Weikang; Li, Luyuan; Kan, Qiuqi; Fu, Hui; Geng, Tuoyu; Li, Tuofan; Wan, Zhimin; Gao, Wei; Shao, Hongxia; Qin, Aijian; Ye, Jianqiang
• Is Part Of: Virulence. Volume 12:Issue 1(2021)
• Page Start: 754
• Page End: 765
• Publication Date: 2021-01-01
• Subjects: FAdV-4 -- Fiber-2 -- KPNA3/4 -- interaction -- gene edition -- pathogenesis -- live-attenuated vaccine; Virulence (Microbiology) -- Periodicals; Bacterial diseases -- Periodicals; Molecular microbiology -- Periodicals; 579.05
• DOI: 10.1080/21505594.2021.1888458
• Languages: English
• ISSNs: 2150-5608

Abstract

ABSTRACT: The outbreaks of hepatitis-hydropericardium syndrome (HPS) caused by the highly pathogenic serotype 4 fowl adenovirus (FAdV-4) have caused a huge economic loss to the poultry industry globally since 2013. Although the Fiber-2 has been identified as a key virulent related factor for FAdV-4, little is known about its molecular basis. In this study, we identified the efficient interaction of the Fiber-2 with the karyopherin alpha 3/4 (KPNA3/4) protein via its N-terminus of 1–40aa. The analysis of the overexpression and knockout of KPNA3/4 showed that KPNA3/4 could efficiently assist the replication of FAdV-4. Moreover, a fiber-2 -edited virus FAV-4_Del with a deletion of 7–40aa in Fiber-2 was rescued through the CRISPR-Cas9 technique. In comparison with the wild type FAdV-4, FAV-4_Del was highly attenuated in vitro and in vivo . Notably, the inoculation of FAV-4_Del in chickens could provide full protection against the lethal challenge with the wild type FAdV-4. All these findings not only give novel insights into the molecular basis for the pathogenesis of Fiber-2 but also provide efficient targets for developing antiviral strategies and live-attenuated vaccine candidates against the highly pathogenic FAdV-4.