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Journal of Virology, June 2007, p. 6664-6668, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.02365-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Emergence of Mammalian Cell-Adapted Vesicular Stomatitis Virus from Persistent Infections of Insect Vector Cells{triangledown}

Isabel S. Novella,1* Bonnie E. Ebendick-Corpus,1 Selene Zárate,1,# and Eric L. Miller2

Department of Medical Microbiology and Immunology, Medical University of Ohio, 3055 Arlington Ave., Toledo, Ohio 43614,1 Department of Integrative Biology, University of Texas at Austin, Austin, Texas 787122

Received 28 November 2006/ Accepted 2 April 2007

Arboviruses (arthropod-borne viruses) represent quintessential generalists, with the ability to infect and perform well in multiple hosts. However, antagonistic pleiotropy imposed a cost during the adaptation to persistent replication of vesicular stomatitis virus in sand fly cells and resulted in strains that initially replicated poorly in hamster cells, even when the virus was allowed to replicate periodically in the latter. Once a debilitated strain started replicating continuously in mammalian cells, fitness increased significantly. Fitness recovery did not entail back mutations or compensatory mutations, but instead, we observed the replacement of persistence-adapted genomes by mammalian cell-adapted strains with a full set of new, unrelated sequence changes. These mammalian cell-adapted genomes were present at low frequencies in the populations with a history of persistence for up to a year and quickly became dominant during mammalian infection, but coexistence was not stable in the long term. Periodic acute replication in mammalian cells likely contributed to extending the survival of minority genomes, but these genomes were also found in strictly persistent populations.


* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, Medical University of Ohio, 3055 Arlington Ave., Toledo, OH 43614. Phone: (419) 383-6442. Fax: (419) 383-3002. E-mail: isabel{at}meduohio.edu

{triangledown} Published ahead of print on 11 March 2007.

# Present address: Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92122.


Journal of Virology, June 2007, p. 6664-6668, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.02365-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.