DOI: 10.1073/pnas.0701397104. The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription

The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription

10.1073/pnas.0701397104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Recent studies indicate that the interaction between rabies virus (RV) phosphoprotein and the dynein light chain 8 (LC8) is essential for RV pathogenesis. Through its association with the dynein motor complex, LC8 has been suggested as a molecular factor that links the viral ribonucleoprotein to the host cell transport system. Recent structural investigations, however, dispute this model. To understand the role of LC8 in RV pathogenesis, we generated recombinant RVs with or without the LC8 binding domain (LC8-BD) deleted from the RV phosphoprotein. Peripheral infection of adult mice showed that removal of the LC8-BD did not inhibit entry into the CNS, although it prevented onset of RV-induced CNS disease. However, deletion of the LC8-BD significantly attenuated viral transcription and replication in the CNS. Studies in RAG2 knockout (KO) mice infected with the same recombinant RVs confirmed this finding and indicated that the adaptive immune system is not a factor in the attenuation of viral replication early in the infection. In cell culture, the deletion of the LC8-BD greatly attenuated growth on neuronal cells whereas the growth pattern on nonneuronal cells remained unchanged. However, deletion of the LC8-BD did not affect production of RV virions. We provide evidence that removal of the LC8-BD decreases primary transcription. In this study, we propose that LC8 does not play a role in the retrograde axonal transport of RV and that the deletion of the LC8-BD impairs the infectivity of the virions by reducing early transcription and replication in neurons.

Bibliography

Tan, G. S., Preuss, M. A. R., Williams, J. C., & Schnell, M. J. (2007). The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription. Proceedings of the National Academy of Sciences, 104(17), 7229â7234.

Authors 4

Gene S. Tan (first)
Mirjam A. R. Preuss (additional)
John C. Williams (additional)
Matthias J. Schnell (additional)

References 50 Referenced 116

Dates

Type	When
Created	18 years, 4 months ago (April 16, 2007, 8:54 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 5:07 p.m.)
Indexed	3 days, 19 hours ago (Aug. 29, 2025, 6:22 a.m.)
Issued	18 years, 4 months ago (April 24, 2007)
Published	18 years, 4 months ago (April 24, 2007)
Published Online	18 years, 4 months ago (April 24, 2007)
Published Print	18 years, 4 months ago (April 24, 2007)

Funders 0

None

BibTeX

@article{Tan_2007, title={The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0701397104}, DOI={10.1073/pnas.0701397104}, number={17}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Tan, Gene S. and Preuss, Mirjam A. R. and Williams, John C. and Schnell, Matthias J.}, year={2007}, month=apr, pages={7229–7234} }

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