Dataset Information

Differential use of importin-? isoforms governs cell tropism and host adaptation of influenza virus.

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-?, 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-?-silenced cells and importin-?-knockout mice, to understand the role of individual importin-? isoforms in adaptation. For efficient virus replication, the polymerase subunit PB2 and the nucleoprotein (NP) of avian viruses required importin-?3, whereas PB2 and NP of mammalian viruses showed importin-?7 specificity. H1N1v replication depended on both, importin-?3 and -?7, suggesting ongoing adaptation of this virus. Thus, differences in importin-? specificity are determinants of host range underlining the importance of the nuclear envelope in interspecies transmission.

SUBMITTER: Gabriel G

PROVIDER: S-EPMC3105303 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus.

Gabriel Gülsah G Klingel Karin K Otte Anna A Thiele Swantje S Hudjetz Ben B Arman-Kalcek Gökhan G Sauter Martina M Shmidt Tatiana T Rother Franziska F Baumgarte Sigrid S Keiner Björn B Hartmann Enno E Bader Michael M Brownlee George G GG Fodor Ervin E Klenk Hans-Dieter HD

Nature communications 20110101

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-α, 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 ...[more]

PMID: 21245837

Similar Datasets

Project description:BackgroundMajority of influenza A viruses reside and circulate among animal populations, seldom infecting humans due to host range restriction. Yet when some avian strains do acquire the ability to overcome species barrier, they might become adapted to humans, replicating efficiently and causing diseases, leading to potential pandemic. With the huge influenza A virus reservoir in wild birds, it is a cause for concern when a new influenza strain emerges with the ability to cross host species barrier, as shown in light of the recent H7N9 outbreak in China. Several influenza proteins have been shown to be major determinants in host tropism. Further understanding and determining host tropism would be important in identifying zoonotic influenza virus strains capable of crossing species barrier and infecting humans.ResultsIn this study, computational models for 11 influenza proteins have been constructed using the machine learning algorithm random forest for prediction of host tropism. The prediction models were trained on influenza protein sequences isolated from both avian and human samples, which were transformed into amino acid physicochemical properties feature vectors. The results were highly accurate prediction models (ACC>96.57; AUC>0.980; MCC>0.916) capable of determining host tropism of individual influenza proteins. In addition, features from all 11 proteins were used to construct a combined model to predict host tropism of influenza virus strains. This would help assess a novel influenza strain's host range capability.ConclusionsFrom the prediction models constructed, all achieved high prediction performance, indicating clear distinctions in both avian and human proteins. When used together as a host tropism prediction system, zoonotic strains could potentially be identified based on different protein prediction results. Understanding and predicting host tropism of influenza proteins lay an important foundation for future work in constructing computation models capable of directly predicting interspecies transmission of influenza viruses. The models are available for prediction at http://fluleap.bic.nus.edu.sg.

Dataset Information

Differential use of importin-? isoforms governs cell tropism and host adaptation of influenza virus.

Publications

Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets