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Open AccessArticle

Three YXXL Sequences of a Bovine Leukemia Virus Transmembrane Protein are Independently Required for Fusion Activity by Controlling Expression on the Cell Membrane

1
Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
2
Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
3
Laboratory of Viral Infectious Diseases, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
4
Live Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
5
Nakamura Laboratory, Baton Zone program, Riken Cluster for Science, Technology and Innovation Hub, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(12), 1140; https://doi.org/10.3390/v11121140
Received: 18 October 2019 / Revised: 5 December 2019 / Accepted: 8 December 2019 / Published: 10 December 2019
(This article belongs to the Section Animal Viruses)
Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia viruses, is the causative agent of enzootic bovine leukosis, the most common neoplastic disease of cattle. The transmembrane subunit of the BLV envelope glycoprotein, gp30, contains three completely conserved YXXL sequences that fit an endocytic sorting motif. The two N-terminal YXXL sequences are reportedly critical for viral infection. However, their actual function in the viral life cycle remains undetermined. Here, we identified the novel roles of each YXXL sequence. Syncytia formation ability was upregulated by a single mutation of the tyrosine (Tyr) residue in any of the three YXXL sequences, indicating that each YXXL sequence is independently able to regulate the fusion event. The alteration resulted from significantly high expression of gp51 on the cell surface, thereby decreasing the amount of gp51 in early endosomes and further revealing that the three YXXL sequences are independently required for internalization of the envelope (Env) protein, following transport to the cell surface. Moreover, the 2nd and 3rd YXXL sequences contributed to Env protein incorporation into the virion by functionally distinct mechanisms. Our findings provide new insights regarding the three YXXL sequences toward the BLV viral life cycle and for developing new anti-BLV drugs. View Full-Text
Keywords: BLV; YXXL sequence; syncytia formation; Env distribution; virion incorporation; internalization; endosome; membrane binding BLV; YXXL sequence; syncytia formation; Env distribution; virion incorporation; internalization; endosome; membrane binding
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Matsuura, R.; Inabe, K.; Otsuki, H.; Kurokawa, K.; Dohmae, N.; Aida, Y. Three YXXL Sequences of a Bovine Leukemia Virus Transmembrane Protein are Independently Required for Fusion Activity by Controlling Expression on the Cell Membrane. Viruses 2019, 11, 1140.

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