title: Tiger frog virus ORF080L protein interacts with LITAF and impairs EGF-induced EGFR degradation.
abstract: Tiger frog virus (TFV) belongs to the genus Ranavirus, family Iridoviridae, and causes severe mortality in commercial cultures in China. TFV ORF080L is a gene homolog of lipopolysaccharide-induced TNF-α factor (LITAF), which is a regulator in endosome-to-lysosome trafficking through its function in the endosomal sorting complex required for transport machinery. The characteristics and biological roles of TFV ORF080L were identified. TFV ORF080L was predicted to encode an 84-amino acid peptide (VP080L). It had high-sequence identity with mammalian LITAF, but lacked the N-terminus of LITAF, which contains two PPXY motifs. Transcription and protein level analyses showed that TFV ORF080L was a late viral gene. Localization in the virons also showed that TFV VP080L was a viral structural protein. Immunofluorescence staining showed that TFV ORF080L was predominantly colocalized with plasma membrane and partly distributed with the late endosome in infected HepG2 cells. SiRNA-mediated TFV ORF080L silencing decreased viral reproduction. Moreover, TFV ORF080L interacted with human/zebrafish LITAF and impaired EGF-induced EGFR degradation, thereby indicating that TFV ORF080L played a role in endosome-to-lysosome trafficking. These findings suggested that TFV ORF080L might negate the function of cellular LITAF to impair endosomal sorting and trafficking. Results provide a clue to the link between the dysregulated endosomal trafficking and iridovirus pathogenesis.
authors.affiliation: MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Yong-Shun
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering/South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, School of Marine, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China; MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Qin
authors.affiliation: Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering/South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, School of Marine, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Mi
authors.affiliation: Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering/South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, School of Marine, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Lin
authors.affiliation: MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Gao
authors.affiliation: MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Weng
authors.affiliation: Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering/South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, School of Marine, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China; MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China. Electronic address: relike2004@sina.com.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Guo
authors.affiliation: MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, 135 Xingang Road West, Guangzhou 510275, PR China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: He
mesh_terms: D000818:Animals; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D059748:Proteolysis / Q000187:drug effects; D017995:Ranavirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D060888:Real-Time Polymerase Chain Reaction; D020539:Sequence Analysis, Protein; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000378:metabolism / Q000494:pharmacology*; D014771:Virion; D014779:Virus Replication
chemical_list: D014409:Tumor Necrosis Factor-alpha; D015678:Viral Structural Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: Endosome-lysosome pathway; Iridovirus; LITAF; Tiger frog virus; Viral replication