Specific interaction of capsid protein and importin-alpha/beta influences West Nile virus production.
West Nile virus (WNV) capsid (C) protein has been shown to enter the nucleus of infected cells. However, the mechanism by which C protein enters the nucleus is unknown. In this study, we have unveiled for the first time that nuclear transport of WNV and Dengue virus C protein is mediated by their direct association with importin-alpha. This interplay is mediated by the consensus sequences of bipartite nuclear localization signal located between amino acid residues 85-101 together with amino acid residues 42 and 43 of C protein. Elucidation of biological significance of importin-alpha/C protein interaction demonstrated that the binding efficiency of this association influenced the nuclear entry of C protein and virus production. Collectively, this study illustrated the molecular mechanism by which the C protein of arthropod-borne flavivirus enters the nucleus and showed the importance of importin-alpha/C protein interaction in the context of flavivirus life-cycle.
Bhuvanakantham
Raghavan
R
Flavivirology Laboratory, Department of Microbiology, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore.
Chong
Mun-Keat
MK
Ng
Mah-Lee
ML
D021581:Active Transport, Cell Nucleus; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication; D014902:West Nile virus / Q000378:metabolism / Q000502:physiology*; D028901:alpha Karyopherins / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
D036022:Capsid Proteins; D019913:Nuclear Localization Signals; D028901:alpha Karyopherins; D028961:beta Karyopherins