title: Nuclear localization and secretion competence are conserved among henipavirus matrix proteins.
abstract: Viruses of the genus Henipavirus of the family Paramyxoviridae are zoonotic pathogens, which have emerged in Southeast Asia, Australia and Africa. Nipah virus (NiV) and Hendra virus are highly virulent pathogens transmitted from bats to animals and humans, while the henipavirus Cedar virus seems to be non-pathogenic in infection studies. The full replication cycle of the Paramyxoviridae occurs in the host cell's cytoplasm, where viral assembly is orchestrated by the matrix (M) protein. Unexpectedly, the NiV-M protein traffics through the nucleus as an essential step to engage the plasma membrane in preparation for viral budding/release. Comparative studies were performed to assess whether M protein nuclear localization is a common feature of the henipaviruses, including the recently sequenced (although not yet isolated) Ghanaian bat henipavirus (Kumasi virus, GH-M74a virus) and Mojiang virus. Live-cell confocal microscopy revealed that nuclear translocation of GFP-fused M protein is conserved between henipaviruses in both human- and bat-derived cell lines. However, the efficiency of M protein nuclear localization and virus-like particle budding competency varied. Additionally, Cedar virus-, Kumasi virus- and Mojiang virus-M proteins were mutated in a bipartite nuclear localization signal, indicating that a key lysine residue is essential for nuclear import, export and induction of budding events, as previously reported for NiV-M. The results of this study suggest that the M proteins of henipaviruses may utilize a similar nucleocytoplasmic trafficking pathway as an essential step during viral replication in both humans and bats.
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Elisabeth C
authors.initials: EC
authors.lastname: McLinton
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Wagstaff
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science & Biotechnology Institute, The University of Melbourne, Victoria 3000, Australia.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Moseley
authors.affiliation: CSIRO Biosecurity Flagship, Australian Animal Health Laboratory, Geelong, Victoria 3219, Australia.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Marsh
authors.affiliation: Programme in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Jans
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.|Present address: Commonwealth Serum Laboratories Limited, Parkville, Victoria 3052, Australia.
authors.forename: Kim G
authors.initials: KG
authors.lastname: Lieu
authors.affiliation: Victorian Infectious Diseases Reference Laboratory, Melbourne Health, The Peter Doherty Institute, Victoria 3000, Australia.|Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Netter
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D045403:Henipavirus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D019913:Nuclear Localization Signals; D021381:Protein Transport; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D022701:Virosomes / Q000235:genetics / Q000378:metabolism
chemical_list: D019913:Nuclear Localization Signals; D014763:Viral Matrix Proteins; D022701:Virosomes