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| Item Type: | Article |
|---|---|
| Title: | Differential use of importin-alpha isoforms governs cell tropism and host adaptation of influenza virus |
| Creators Name: | Gabriel, G., Klingel, K., Otte, A., Thiele, S., Hudjetz, B., Arman-Kalcek, G., Sauter, M., Shmidt, T., Rother, F., Baumgarte, S., Keiner, B., Hartmann, E., Bader, M., Brownlee, G.G., Fodor, E. and Klenk, H.D. |
| Abstract: | Influenza A viruses are a threat to humans due to their ability to cross species barriers, as illustrated by the 2009 H1N1v pandemic and sporadic H5N1 transmissions. Interspecies transmission requires adaptation of the viral polymerase to importin-alpha, a cellular protein that mediates transport into the nucleus where transcription and replication of the viral genome takes place. In this study, we analysed replication, host specificity and pathogenicity of avian and mammalian influenza viruses, in importin-alpha-silenced cells and importin-alpha-knockout mice, to understand the role of individual importin-alpha isoforms in adaptation. For efficient virus replication, the polymerase subunit PB2 and the nucleoprotein (NP) of avian viruses required importin-alpha3, whereas PB2 and NP of mammalian viruses showed importin-alpha7 specificity. H1N1v replication depended on both, importin-alpha3 and -alpha7, suggesting ongoing adaptation of this virus. Thus, differences in importin-alpha specificity are determinants of host range underlining the importance of the nuclear envelope in interspecies transmission. |
| Keywords: | Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 2 |
| Number: | 1 |
| Page Range: | 156 |
| Date: | January 2011 |
| Official Publication: | https://doi.org/10.1038/ncomms1158 |
| PubMed: | View item in PubMed |
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