title: Replacement of the hepatitis E virus ORF3 protein PxxP motif with heterologous late domain motifs affects virus release via interaction with TSG101.
abstract: The ORF3 protein of hepatitis E virus (HEV) contains a "PSAP" amino acid late domain motif, which allows for interaction with the endosomal sorting complexes required for transport (ESCRT) pathway aiding virion release. Late domain motifs are interchangeable with other viral late domain motifs in several enveloped viruses, however, it remains unknown whether HEV shares this functional interchangeability and what implications this might have on viral replication. In this study, by substituting heterologous late domain motifs (PPPY, YPDL, and PSAA) for the HEV ORF3 late domain (PSAP), we demonstrated that deviation from the PSAP motif reduces virus release as measured by viral RNA in culture media. Virus release could not be restored by insertion of a heterologous late domain motif or by supplying wild-type ORF3 in trans, suggesting that the HEV PSAP motif is required for viral exit which cannot be bypassed by the use of alternative heterologous late domains.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Kenney
authors.affiliation: Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.
authors.forename: Jacquelyn L
authors.initials: JL
authors.lastname: Wentworth
authors.affiliation: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA.
authors.forename: Connie L
authors.initials: CL
authors.lastname: Heffron
authors.affiliation: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Electronic address: xjmeng@vt.edu.
authors.forename: Xiang-Jin
authors.initials: XJ
authors.lastname: Meng
mesh_terms: D020816:Amino Acid Motifs; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D016751:Hepatitis E / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D016752:Hepatitis E virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release; D014779:Virus Replication; D000099177:Tsg101 Protein
chemical_list: D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D014157:Transcription Factors; D014764:Viral Proteins; D000099177:Tsg101 Protein; C400973:ORF3 protein, Hepatitis E virus
keywords: Hepatitis E virus (HEV); Late domain; Open reading frame 3 (ORF3); PxxP motif; Virus release