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Published on: November 4, 2015
KIF5B-mediated internalization of FMDV promotes virus infection
Wei Zhang1, Fan Yang1, Yang Yang1
1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou 730046, China.
Abstract:
Foot-and-mouth disease (FMD) is a highly contagious and economically important disease, which is caused by the FMD virus (FMDV). Although the cell receptor for FMDV has been identified, the specific mechanism of FMDV internalization after infection remains unknown. In this study, we found that kinesin family member 5B (KIF5B) plays a vital role during FMDV internalization. Moreover, we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation (Co-IP) and co-localization in FMDV-infected cells. In particular, the stalk [amino acids (aa) 413-678] domain of KIF5B was indispensable for KIF5B-VP1 interaction. Moreover, overexpression of KIF5B dramatically enhanced FMDV replication; consistently, knockdown or knockout of KIF5B suppressed FMDV replication. Furthermore, we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating. KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection. In conclusion, our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport. This study may provide a new therapeutic target for developing FMDV antiviral drugs.
Insights
Kinesin family member 5B (KIF5B) is crucial for foot-and-mouth disease virus (FMDV) entry into cells. This discovery offers a potential new target for developing antiviral drugs against FMDV.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Foot-and-mouth disease (FMD) is a highly contagious viral disease with significant economic impact.
- The precise mechanism of FMD virus (FMDV) cell entry remains incompletely understood, despite identification of its cellular receptor.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying FMDV internalization into host cells.
- To identify host factors involved in FMDV infection and replication.
Main Methods:
- Co-immunoprecipitation (Co-IP) to confirm protein interactions.
- Co-localization studies in infected cells.
- KIF5B overexpression, knockdown, and knockout experiments.
- Analysis of FMDV replication and viral particle transport.
Main Results:
- Kinesin family member 5B (KIF5B) was identified as a key host factor in FMDV internalization.
- Direct interaction between KIF5B and FMDV structural protein VP1 was confirmed, specifically involving the KIF5B stalk domain.
- KIF5B overexpression enhanced FMDV replication, while KIF5B depletion suppressed it.
- KIF5B regulates clathrin uncoating and facilitates viral particle transport to endosomes, promoting FMDV entry.
Conclusions:
- KIF5B plays a critical role in FMDV internalization by regulating clathrin uncoating and intracellular transport.
- The interaction between KIF5B and FMDV VP1 is essential for efficient viral entry and replication.
- KIF5B represents a potential novel therapeutic target for FMDV antiviral drug development.
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