A filovirus-unique region of ebola virus nucleoprotein confers aberrant migration and mediates its incorporation into virions

Wei Shi, Yue Huang, Mark Sutton-Smith, Berangere Tissot, Maria Panico, Howard R. Morris, Anne Dell, Stuart M. Haslam, Jeffrey Boyington, Barney S. Graham, Zhi Yong Yang, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6190-6199
Number of pages10
JournalJournal of Virology
Volume82
Issue number13
DOIs
StatePublished - Jul 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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