title: Residues in the hendra virus fusion protein transmembrane domain are critical for endocytic recycling.
abstract: Hendra virus is a highly pathogenic paramyxovirus classified as a biosafety level four agent. The fusion (F) protein of Hendra virus is critical for promoting viral entry and cell-to-cell fusion. To be fusogenically active, Hendra virus F must undergo endocytic recycling and cleavage by the endosomal/lysosomal protease cathepsin L, but the route of Hendra virus F following internalization and the recycling signals involved are poorly understood. We examined the intracellular distribution of Hendra virus F following endocytosis and showed that it is primarily present in Rab5- and Rab4-positive endosomal compartments, suggesting that cathepsin L cleavage occurs in early endosomes. Hendra virus F transmembrane domain (TMD) residues S490 and Y498 were found to be important for correct Hendra virus F recycling, with the hydroxyl group of S490 and the aromatic ring of Y498 important for this process. In addition, changes in association of isolated Hendra virus F TMDs correlated with alterations to Hendra virus F recycling, suggesting that appropriate TMD interactions play an important role in endocytic trafficking.
authors.affiliation: Department of Molecular and Cellular Biochemistrya and Center for Structural Biology,b University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Andreea
authors.initials: A
authors.lastname: Popa
authors.forename: James R
authors.initials: JR
authors.lastname: Carter
authors.forename: Stacy E
authors.initials: SE
authors.lastname: Smith
authors.forename: Lance
authors.initials: L
authors.lastname: Hellman
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fried
authors.forename: Rebecca Ellis
authors.initials: RE
authors.lastname: Dutch
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D045404:Hendra Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045464:Henipavirus Infections / Q000503:physiopathology* / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016415:Sequence Alignment; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D014760:Viral Fusion Proteins