AUF1 p45 Promotes West Nile Virus Replication by an RNA Chaperone Activity That Supports Cyclization of the Viral Genome
| Autor: | Sebastian Ulbert, Rene Geissler, Hauke Lilie, Ralph Golbik, Uwe G. Liebert, Sven-Erik Behrens, Susann Friedrich, Tobias Schmidt, Stefan Chabierski |
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| Rok vydání: | 2014 |
| Předmět: |
Gene Expression Regulation
Viral viruses Immunology RNA-dependent RNA polymerase Genome Viral Biology Virus Replication Microbiology VP40 Viral entry Cell Line Tumor Virology Viral structural protein Humans Protein Isoforms Heterogeneous Nuclear Ribonucleoprotein D0 Heterogeneous-Nuclear Ribonucleoprotein D Ribonucleoprotein Genetics Binding Sites virus diseases RNA RNA Circular Genome Replication and Regulation of Viral Gene Expression Viral replication Insect Science Helper virus Host-Pathogen Interactions Hepatocytes RNA Viral West Nile virus Molecular Chaperones Protein Binding |
| Zdroj: | Journal of Virology. 88:11586-11599 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | A central aspect of current virology is to define the function of cellular proteins (host factors) that support the viral multiplication process. This study aimed at characterizing cellular proteins that assist the RNA replication process of the prevalent human pathogen West Nile virus (WNV). Using in vitro and cell-based approaches, we defined the p45 isoform of AU-rich element RNA-binding protein 1 (AUF1) as a host factor that enables efficient WNV replication. It was demonstrated that AUF1 p45 has an RNA chaperone activity, which aids the structural rearrangement and cyclization of the WNV RNA that is required by the viral replicase to initiate RNA replication. The obtained data suggest the RNA chaperone activity of AUF1 p45 is an important determinant of the WNV life cycle. IMPORTANCE In this study, we identified a cellular protein, AUF1 (also known as heterogeneous ribonucleoprotein D [hnRNPD]), acting as a helper (host factor) of the multiplication process of the important human pathogen West Nile virus. Several different variants of AUF1 exist in the cell, and one variant, AUF1 p45, was shown to support viral replication most significantly. Interestingly, we obtained a set of experimental data indicating that a main function of AUF1 p45 is to modify and thus prepare the West Nile virus genome in such a way that the viral enzyme that generates progeny genomes is empowered to do this considerably more efficiently than in the absence of the host factor. The capability of AUF1 p45 to rearrange the West Nile virus genome was thus identified to be an important aspect of a West Nile virus infection. |
| Databáze: | OpenAIRE |
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