Internally deleted WNV genomes isolated from exotic birds in New Mexico: Function in cells, mosquitoes, and mice

Kendra N. Pesko, Kelly A. Fitzpatrick, Elizabeth M. Ryan, Pei Yong Shi, Bo Zhang, Niall J. Lennon, Ruchi M. Newman, Matthew R. Henn, Gregory D. Ebel

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Most RNA viruses exist in their hosts as a heterogeneous population of related variants. Due to error prone replication, mutants are constantly generated which may differ in individual fitness from the population as a whole. Here we characterize three WNV isolates that contain, along with full-length genomes, mutants with large internal deletions to structural and nonstructural protein-coding regions. The isolates were all obtained from lorikeets that died from WNV at the Rio Grande Zoo in Albuquerque, NM between 2005 and 2007. The deletions are approximately 2. kb, in frame, and result in the elimination of the complete envelope, and portions of the prM and NS-1 proteins. In Vero cell culture, these internally deleted WNV genomes function as defective interfering particles, reducing the production of full-length virus when introduced at high multiplicities of infection. In mosquitoes, the shortened WNV genomes reduced infection and dissemination rates, and virus titers overall, and were not detected in legs or salivary secretions at 14 or 21. days post-infection. In mice, inoculation with internally deleted genomes did not attenuate pathogenesis relative to full-length or infectious clone derived virus, and shortened genomes were not detected in mice at the time of death. These observations provide evidence that large deletions may occur within flavivirus populations more frequently than has generally been appreciated and suggest that they impact population phenotype minimally. Additionally, our findings suggest that highly similar mutants may frequently occur in particular vertebrate hosts.

Original languageEnglish (US)
Pages (from-to)10-17
Number of pages8
JournalVirology
Volume427
Issue number1
DOIs
StatePublished - May 25 2012
Externally publishedYes

Keywords

  • Defective interfering particles
  • Genetic variation
  • West Nile virus

ASJC Scopus subject areas

  • Virology

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    Pesko, K. N., Fitzpatrick, K. A., Ryan, E. M., Shi, P. Y., Zhang, B., Lennon, N. J., Newman, R. M., Henn, M. R., & Ebel, G. D. (2012). Internally deleted WNV genomes isolated from exotic birds in New Mexico: Function in cells, mosquitoes, and mice. Virology, 427(1), 10-17. https://doi.org/10.1016/j.virol.2012.01.028