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Journal of Virology, August 2005, p. 10300-10307, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10300-10307.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Ebola Virus VP40 Late Domains Are Not Essential for Viral Replication in Cell Culture

Gabriele Neumann,1 Hideki Ebihara,2,5 Ayato Takada,2 Takeshi Noda,2 Darwyn Kobasa,3 Luke D. Jasenosky,1 Shinji Watanabe,1 Jin H. Kim,1 Heinz Feldmann,4 and Yoshihiro Kawaoka1,2,5*

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, Wisconsin 53706,1 Institute of Medical Sciences, University of Tokyo, Tokyo 108-8639, Japan,2 Viral Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada and Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 3R2, Canada,3 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada and Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 3R2, Canada,4 CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan5

Received 6 February 2005/ Accepted 10 May 2005

Ebola virus particle formation and budding are mediated by the VP40 protein, which possesses overlapping PTAP and PPXY late domain motifs (7-PTAPPXY-13). These late domain motifs have also been found in the Gag proteins of retroviruses and the matrix proteins of rhabdo- and arenaviruses. While in vitro studies suggest a critical role for late domain motifs in the budding of these viruses, including Ebola virus, it remains unclear as to whether the VP40 late domains play a role in Ebola virus replication. Alteration of both late domain motifs drastically reduced VP40 particle formation in vitro. However, using reverse genetics, we were able to generate recombinant Ebola virus containing mutations in either or both of the late domains. Viruses containing mutations in one or both of their late domain motifs were attenuated by one log unit. Transmission and scanning electron microscopy did not reveal appreciable differences between the mutant and wild-type viruses released from infected cells. These findings indicate that the Ebola VP40 late domain motifs enhance virus replication but are not absolutely required for virus replication in cell culture.

* Corresponding author. Mailing address: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Dr., Madison, WI 53706. Phone: (608) 265-4925. Fax: (608) 265-5622. E-mail: kawaokay{at}svm.vetmed.wisc.edu.

Journal of Virology, August 2005, p. 10300-10307, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10300-10307.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Halfmann, P., Ebihara, H., Marzi, A., Hatta, Y., Watanabe, S., Suresh, M., Neumann, G., Feldmann, H., Kawaoka, Y. (2009). Replication-Deficient Ebolavirus as a Vaccine Candidate. J. Virol. 83: 3810-3815 [Abstract] [Full Text]  
  • Okumura, A., Pitha, P. M., Harty, R. N. (2008). ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity. Proc. Natl. Acad. Sci. USA 105: 3974-3979 [Abstract] [Full Text]  
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