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Published on: November 1, 2011
Morbillivirus nucleoprotein possesses a novel nuclear localization signal and a CRM1-independent nuclear export
Hiroki Sato1, Munemitsu Masuda, Ryuichi Miura
1Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Abstract:
Morbilliviruses, which belong to the Mononegavirales, replicate its RNA genome in the cytoplasm of the host cell. However, they also form characteristic intranuclear inclusion bodies, consisting of nucleoprotein (N), in infected cells. To analyze the mechanisms of nucleocytoplasmic transport of N protein, we characterized the nuclear localization (NLS) and nuclear export (NES) signals of canine distemper virus (CDV) N protein by deletion mutation and alanine substitution of the protein. The NLS has a novel leucine/isoleucine-rich motif (TGILISIL) at positions 70-77, whereas the NES is composed of a leucine-rich motif (LLRSLTLF) at positions 4-11. The NLS and NES of the N proteins of other morbilliviruses, that is, measles virus (MV) and rinderpest virus (RPV), were also analyzed. The NLS of CDV-N protein is conserved at the same position in MV-N protein, whereas the NES of MV-N protein is located in the C-terminal region. The NES of RPV-N protein is also located at the same position as CDV-N protein, whereas the NLS motif is present not only at the same locus as CDV-N protein but also at other sites. Interestingly, the nuclear export of all these N proteins appears to proceed via a CRM1-independent pathway.
Insights
Canine distemper virus (CDV) nucleoprotein (N) transport involves novel nuclear localization and export signals. These signals differ across morbilliviruses, but nuclear export is CRM1-independent for all.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Morbilliviruses, including canine distemper virus (CDV), replicate RNA genomes in the cytoplasm.
- Morbillivirus-infected cells exhibit intranuclear inclusion bodies composed of nucleoprotein (N).
Purpose of the Study:
- To elucidate the mechanisms of nucleocytoplasmic transport of the CDV N protein.
- To identify and characterize the nuclear localization signals (NLS) and nuclear export signals (NES) of CDV N protein.
- To compare NLS and NES in other morbilliviruses, such as measles virus (MV) and rinderpest virus (RPV).
Main Methods:
- Deletion mutation and alanine substitution analyses were performed on the CDV N protein.
- Characterization of NLS and NES motifs.
- Comparative analysis of NLS and NES across different morbilliviruses.
Main Results:
- A novel leucine/isoleucine-rich NLS (TGILISIL) was identified at positions 70-77 of CDV N protein.
- A leucine-rich NES (LLRSLTLF) was identified at positions 4-11 of CDV N protein.
- Conserved NLS in MV-N protein, divergent NES in MV-N protein, and conserved NES in RPV-N protein were observed.
- All analyzed morbillivirus N proteins utilize a CRM1-independent pathway for nuclear export.
Conclusions:
- The CDV N protein possesses distinct NLS and NES motifs critical for its nucleocytoplasmic transport.
- Significant variations in NLS and NES localization exist among different morbilliviruses.
- Nuclear export of morbillivirus N proteins occurs independently of the CRM1 pathway.
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