tetano
Editor, Senior Moderator
Published ahead of print 13 June 2012, doi: 10.1128/JVI.00789-12 JVI.00789-12
Doroth?e Moisy1,2,3,
Sergiy V. Avilov4,5,
Yves Jacob6,
Brid M. Laoide7,
Xingyi Ge1,2,3,
Florence Baudin5,8,
Nadia Naffakh1,2,3,* and
Jean-Luc Jestin2,9
1Institut Pasteur, Unit? de G?n?tique Mol?culaire des Virus ? ARN, D?partement de Virologie, F-75015 Paris, France
2CNRS, URA3015, F-75015 Paris, France
3Universit? Paris Diderot, Sorbonne Paris Cit?, Unit? de G?n?tique Mol?culaire des Virus ? ARN, F-75015 Paris, France
4European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
5Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMI 3265, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
6Institut Pasteur, Unit? de G?n?tique, Papillomavirus et Cancer Humain, D?partement de Virologie, F-75015 Paris, France
7Institut Pasteur, Unit? de G?n?tique et Biochimie du D?veloppement, F-75015 Paris, France
8European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
9Institut Pasteur, Unit? de Virologie Structurale, D?partement de Virologie, F-75015 Paris, France
ABSTRACT
Influenza virus has evolved replication strategies that hijack host cell pathways. To uncover interactions between viral macromolecules and host proteins, we applied a phage display strategy. A library of human cDNA expression products displayed on filamentous phages was submitted to affinity selection for influenza viral ribonucleoproteins (vRNPs). High-Mobility-Group Box (HMGB) proteins were found to bind to the nucleoprotein (NP) component of vRNPs. HMGB1 and HMGB2 bind directly to the purified NP in the absence of viral RNA, and the HMG Box A domain is sufficient to bind the NP. We show that HMGB1 associates with the viral NP in the nucleus of infected cells, promotes viral growth, and enhances the activity of the viral polymerase. The presence of a functional HMGB1 DNA-binding site is required to enhance influenza virus replication. Glycyrrhizin, which reduces HMGB1 binding to DNA, inhibits influenza virus polymerase activity. Our data show that the HMGB1 protein can play a significant role in intranuclear replication of influenza viruses, thus extending previous findings on Bornavirus and on a number of DNA viruses.
http://jvi.asm.org/content/early/2012/06/08/JVI.00789-12.abstract
Doroth?e Moisy1,2,3,
Sergiy V. Avilov4,5,
Yves Jacob6,
Brid M. Laoide7,
Xingyi Ge1,2,3,
Florence Baudin5,8,
Nadia Naffakh1,2,3,* and
Jean-Luc Jestin2,9
1Institut Pasteur, Unit? de G?n?tique Mol?culaire des Virus ? ARN, D?partement de Virologie, F-75015 Paris, France
2CNRS, URA3015, F-75015 Paris, France
3Universit? Paris Diderot, Sorbonne Paris Cit?, Unit? de G?n?tique Mol?culaire des Virus ? ARN, F-75015 Paris, France
4European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
5Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMI 3265, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
6Institut Pasteur, Unit? de G?n?tique, Papillomavirus et Cancer Humain, D?partement de Virologie, F-75015 Paris, France
7Institut Pasteur, Unit? de G?n?tique et Biochimie du D?veloppement, F-75015 Paris, France
8European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
9Institut Pasteur, Unit? de Virologie Structurale, D?partement de Virologie, F-75015 Paris, France
ABSTRACT
Influenza virus has evolved replication strategies that hijack host cell pathways. To uncover interactions between viral macromolecules and host proteins, we applied a phage display strategy. A library of human cDNA expression products displayed on filamentous phages was submitted to affinity selection for influenza viral ribonucleoproteins (vRNPs). High-Mobility-Group Box (HMGB) proteins were found to bind to the nucleoprotein (NP) component of vRNPs. HMGB1 and HMGB2 bind directly to the purified NP in the absence of viral RNA, and the HMG Box A domain is sufficient to bind the NP. We show that HMGB1 associates with the viral NP in the nucleus of infected cells, promotes viral growth, and enhances the activity of the viral polymerase. The presence of a functional HMGB1 DNA-binding site is required to enhance influenza virus replication. Glycyrrhizin, which reduces HMGB1 binding to DNA, inhibits influenza virus polymerase activity. Our data show that the HMGB1 protein can play a significant role in intranuclear replication of influenza viruses, thus extending previous findings on Bornavirus and on a number of DNA viruses.
http://jvi.asm.org/content/early/2012/06/08/JVI.00789-12.abstract