Nucleocytoplasmic trafficking of Nipah virus W protein involves multiple discrete interactions with the nuclear import and export machinery.
Paramyxoviruses replicate in the cytoplasm with no obvious requirement to interact with the nucleus. Nevertheless, the W protein of the highly lethal bat-borne paramyxovirus Nipah virus (NiV) is known to undergo specific targeting to the nucleus, mediated by a single nuclear localisation signal (NLS) within the C-terminal domain. Here, we report for the first time that additional sites modulate nucleocytoplasmic localisation of W. We show that the N-terminal domain interacts with importin α1 and contributes to nuclear accumulation of W, indicative of a novel N-terminal NLS. We also find that W undergoes exportin-1 mediated nuclear export, dependent on a leucine at position 174. Together, these data enable significant revision of the generally accepted model of W trafficking, with implications for understanding of the mechanisms of NiV immune evasion.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia.
Michelle D
MD
Audsley
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia.
David A
DA
Jans
Department of Biochemistry and Molecular Biology, BIO21 Molecular Science and Biotechnology Institute, 30 Flemington Road, The University of Melbourne, VIC, 3010, Australia. Electronic address: gregory.moseley@unimelb.edu.au.
Gregory W
GW
Moseley
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D007930:Leucine / Q000737:chemistry; D045405:Nipah Virus; D019913:Nuclear Localization Signals / Q000378:metabolism; D010766:Phosphorylation; D000072417:Protein Domains; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism*; D000097606:Exportin 1 Protein
D049452:Green Fluorescent Proteins; D028884:Karyopherins; D007930:Leucine; D019913:Nuclear Localization Signals; D018160:Receptors, Cytoplasmic and Nuclear; D014764:Viral Proteins; D000097606:Exportin 1 Protein; C501252:W protein, Nipah virus
Exportin; Importin; Nipah virus; Nuclear transport; Paramyxovirus; W protein