Functional involvement of a novel Nedd4-like ubiquitin ligase on retrovirus budding.
In this study, we have identified a novel Nedd4-like ubiquitin ligase, BUL1, as the host factor involved in budding of type D retrovirus Mason-Pfizer monkey virus (M-PMV). Overexpression of BUL1 enhanced virus particle release, while a BUL1 mutant in which a W to G substitution was introduced into a WW domain, W791G, lost the ability to bind to the viral Gag protein and abolished its ability to mediate virus budding. In addition, a fragment of BUL1 containing only the WW domains inhibited virus budding in a dominant negative manner. These results, together with previous findings, indicate that the M-PMV Gag L domain interacts with the BUL1 WW domain and that this interaction is essential for virus budding. Our observations provide new insights into the mechanism of virus budding, and could be useful in establishing new antiviral strategies targeted at progeny virus release from a host cell.
Yasuda
Jiro
J
Division of Molecular Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Hunter
Eric
E
Nakao
Mitsuyoshi
M
Shida
Hisatoshi
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D016093:Mason-Pfizer monkey virus / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D000075702:Nedd4 Ubiquitin Protein Ligases; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C099939:BUL1 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D014764:Viral Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; D044767:Ubiquitin-Protein Ligases; D008025:Ligases