The YLDL sequence within Sendai virus m protein is critical for budding of virus-like particles and interacts with Alix/AIP1 independently of C protein

Irie Takashi

Shimazu Yukie

Yoshida Tetsuya

Sakaguchi Takemasa

Journal of Virology

For many enveloped viruses, cellular multivesicular body (MVB) sorting machinery has been reported to be utilized for efficient viral budding. Matrix and Gag proteins have been shown to contain one or two L-domain motifs (PPxY, PT/SAP, YPDL, and FPIV), some of which interact specifically with host cellular proteins involved in multivesicular body sorting, which are recruited to the viral budding site. However, for many enveloped viruses, L-domain motifs have not yet been identified, and the involvement of MVB sorting machinery in viral budding is still unknown. Here we show that both Sendai virus (SeV) matrix protein M and accessory protein C contribute to virus budding by physically interacting with Alix/AIP1. A YLDL sequence within the M protein showed L-domain activity, and its specific interaction with the N-terminus of Alix/AIP1 (1-211) was important for the budding of virus-like particles (VLPs) of M protein. In addition, M-VLP budding was inhibited by the overexpression of some deletion mutants of Alix/AIP1 and depletion of endogenous Alix/AIP1 using specific siRNAs. The YLDL sequence was not replaceable by other L-domain motifs, such as PPxY and PT/SAP, and even YPxL. C protein was also able to physically interact with the N-terminus of Alix/AIP1 (212-357) and enhanced M-VLP budding independently of M-Alix/AIP1 interaction, although it was not released from the transfected cells itself. Our results suggest that the interaction of multiple viral proteins with Alix/AIP1 may enhance the efficiency of the utilization of cellular MVB sorting machinery for efficient SeV budding.

Medical sciences [ 490 ]

eng

American Society for Microbiology

Copyright (c) 2007 American Society for Microbiology

[ISSN] 0022-538X

[DOI] 10.1128/JVI.02218-06

[NCID] AA00708779

[DOI] http://dx.doi.org/10.1128/JVI.02218-06