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Investigation of clade B New World arenavirus tropism by using chimeric GP1 proteins.

ABSTRACT: Clade B of the New World arenaviruses contains both pathogenic and nonpathogenic members, whose surface glycoproteins (GPs) are characterized by different abilities to use the human transferrin receptor type 1 (hTfR1) protein as a receptor. Using closely related pairs of pathogenic and nonpathogenic viruses, we investigated the determinants of the GP1 subunit that confer these different characteristics. We identified a central region (residues 85 to 221) in the Guanarito virus GP1 that was sufficient to interact with hTfR1, with residues 159 to 221 being essential. The recently solved structure of part of the Machupo virus GP1 suggests an explanation for these requirements.

SUBMITTER: Martin VK

PROVIDER: S-EPMC2798354 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Investigation of clade B New World arenavirus tropism by using chimeric GP1 proteins.

Martin Vanessa K VK Droniou-Bonzom Magali E ME Reignier Therese T Oldenburg Jill E JE Cox Alex U AU Cannon Paula M PM

Journal of virology 20091104 2

Clade B of the New World arenaviruses contains both pathogenic and nonpathogenic members, whose surface glycoproteins (GPs) are characterized by different abilities to use the human transferrin receptor type 1 (hTfR1) protein as a receptor. Using closely related pairs of pathogenic and nonpathogenic viruses, we investigated the determinants of the GP1 subunit that confer these different characteristics. We identified a central region (residues 85 to 221) in the Guanarito virus GP1 that was suffi ...[more]

PMID: 19889757

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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

Investigation of clade B New World arenavirus tropism by using chimeric GP1 proteins.

Publications

Investigation of clade B New World arenavirus tropism by using chimeric GP1 proteins.

Similar Datasets

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