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Journal of Virology, January 2009, p. 552-561, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01921-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The p14 FAST Protein of Reptilian Reovirus Increases Vesicular Stomatitis Virus Neuropathogenesis{triangledown}

Christopher W. Brown,1,2,{dagger} Kyle B. Stephenson,3,{dagger} Stephen Hanson,3 Michael Kucharczyk,3 Roy Duncan,4 John C. Bell,2 and Brian D. Lichty3*

Ottawa Health Research Institute, Department of Microbiology and Immunology, University of Ottawa, Ontario, Canada,1 Department of Orthopaedic Surgery, University of Ottawa, Ontario, Canada,2 Department of Medical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada,3 Departments of Microbiology and Immunology and Paediatrics, Dalhousie University, Halifax, Nova Scotia, Canada4

Received 11 September 2008/ Accepted 19 October 2008

The fusogenic orthoreoviruses express nonstructural fusion-associated small transmembrane (FAST) proteins that induce cell-cell fusion and syncytium formation. It has been speculated that the FAST proteins may serve as virulence factors by promoting virus dissemination and increased or altered cytopathology. To directly test this hypothesis, the gene encoding the p14 FAST protein of reptilian reovirus was inserted into the genome of a heterologous virus that does not naturally form syncytia, vesicular stomatitis virus (VSV). Expression of the p14 FAST protein by the VSV/FAST recombinant gave the virus a highly fusogenic phenotype in cell culture. The growth of this recombinant fusogenic VSV strain was unaltered in vitro but was significantly enhanced in vivo. The VSV/FAST recombinant consistently generated higher titers of virus in the brains of BALB/c mice after intranasal or intravenous infection compared to the parental VSV/green fluorescent protein (GFP) strain that expresses GFP in place of p14. The VSV/FAST recombinant also resulted in an increased incidence of hind-limb paralysis, it infected a larger volume of brain tissue, and it induced more extensive neuropathology, thus leading to a lower maximum tolerable dose than that for the VSV/GFP parental virus. In contrast, an interferon-inducing mutant of VSV expressing p14 was still attenuated, indicating that this interferon-inducing phenotype is dominant to the fusogenic properties conveyed by the FAST protein. Based on this evidence, we conclude that the reovirus p14 FAST protein can function as a bona fide virulence factor.

* Corresponding author. Mailing address: Centre for Gene Therapeutics, McMaster University, 1200 Main St., W, MDCL-5023, Hamilton, Ontario L8N 3Z5, Canada. Phone: (905) 525-9140, ext. 22478. Fax: (905) 546-9940. E-mail: lichtyb{at}mcmaster.ca

{triangledown} Published ahead of print on 29 October 2008.

{dagger} C.W.B. and K.B.S. contributed equally to this study.

Journal of Virology, January 2009, p. 552-561, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01921-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Barry, C., Duncan, R. (2009). Multifaceted Sequence-Dependent and -Independent Roles for Reovirus FAST Protein Cytoplasmic Tails in Fusion Pore Formation and Syncytiogenesis. J. Virol. 83: 12185-12195 [Abstract] [Full Text]  
  • Racine, T., Hurst, T., Barry, C., Shou, J., Kibenge, F., Duncan, R. (2009). Aquareovirus Effects Syncytiogenesis by Using a Novel Member of the FAST Protein Family Translated from a Noncanonical Translation Start Site. J. Virol. 83: 5951-5955 [Abstract] [Full Text]  


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