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Journal of Virology, July 2008, p. 6190-6199, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.02731-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Filovirus-Unique Region of Ebola Virus Nucleoprotein Confers Aberrant Migration and Mediates Its Incorporation into Virions{triangledown}

Wei Shi,1 Yue Huang,1,{dagger} Mark Sutton-Smith,2 Berangere Tissot,2 Maria Panico,2 Howard R. Morris,2,3 Anne Dell,2 Stuart M. Haslam,2 Jeffrey Boyington,1 Barney S. Graham,1 Zhi-Yong Yang,1 and Gary J. Nabel1*

Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005,1 Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College, London SW7 2AZ, United Kingdom,2 M-Scan, Ltd., 3 Millars Business Centre, Fishponds Close, Wokingham RG41 2TZ, United Kingdom3

Received 22 December 2007/ Accepted 1 April 2008

The Ebola virus nucleoprotein (NP) is an essential component of the nucleocapsid, required for filovirus particle formation and replication. Together with virion protein 35 (VP35) and VP24, this gene product gives rise to the filamentous nucleocapsid within transfected cells. Ebola virus NP migrates aberrantly, with an apparent molecular mass of 115 kDa, although it is predicted to encode an ~85-kDa protein. In this report, we show that two domains of this protein determine this aberrant migration and that this region mediates its incorporation into virions. These regions, amino acids 439 to 492 and amino acids 589 to 739, alter the mobility of Ebola virus NP by sodium dodecyl sulfate-polyacrylamide gel electrophoresis by 5 and 15 kDa, respectively, and confer similar effects on a heterologous protein, LacZ, in a position-independent fashion. Furthermore, when coexpressed with VP40, VP35, and VP24, this region mediated incorporation of NP into released viruslike particles. When fused to chimeric paramyxovirus NPs derived from measles or respiratory syncytial virus, this domain directed these proteins into the viruslike particle. The COOH-terminal NP domain comprises a conserved highly acidic region of NP with predicted disorder, distinguishing Ebola virus NPs from paramyxovirus NPs. The acidic character of this domain is likely responsible for its aberrant biochemical properties. These findings demonstrate that this region is essential for the assembly of the filamentous nucleocapsids that give rise to filoviruses.

* Corresponding author. Mailing address: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Rm. 4502, MSC-3005, 40 Convent Dr., Bethesda, MD 20892-3005. Phone: (301) 496-1852. Fax: (301) 480-0274. E-mail: gnabel{at}nih.gov

{triangledown} Published ahead of print on 16 April 2008.

{dagger} Deceased.

Journal of Virology, July 2008, p. 6190-6199, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.02731-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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