Investigation for signals and host factors related to paramyxovirus budding.

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In the present project, we obtained the results described below.Firstly, we established a system to generate virus-like particles (VLPs) similar to Sendai virus (SeV) by co-transfecting multiple viral proteins. By using the system, we found that the accessory C protein had an ability to facilitate VLP release. We further demonstrated that the C protein interacted a host factor, AIP1/Alix, and that the interaction was essential for the VLP facilitation.Secondly, we confirmed that the M protein is a driving force for the particle release from cells, and we identified a late domain motif in the M protein, which was further shown to interact with AIP1/Alix. Neither Tsg101 nor Nedd4 appeared to be involved in the M protein function, but ubiquitin and Vps4A were involved in it.Thus, both of the M and C proteins are important for virus budding probably by interacting AIP1/Alix. The interaction was presumed to recruit the endosome-sorting complex required for transport (ESCRT) to virus budding. We further identified amino acid motifs for the interaction between the SeV proteins and AIP/Alix, and will generate viruses carrying the mutations incompetent to binding with AIP1/Alix to confirm and extend our results. As described, viral proteins important virus budding, viral protein motifs for the function, and related host factors are being clarified.