TY - JOUR
T1 - Internally deleted WNV genomes isolated from exotic birds in New Mexico
T2 - Function in cells, mosquitoes, and mice
AU - Pesko, Kendra N.
AU - Fitzpatrick, Kelly A.
AU - Ryan, Elizabeth M.
AU - Shi, Pei Yong
AU - Zhang, Bo
AU - Lennon, Niall J.
AU - Newman, Ruchi M.
AU - Henn, Matthew R.
AU - Ebel, Gregory D.
N1 - Funding Information:
The authors would like to thank Eleanor Deardorff, Doug Brackney, Kathy Hanley and Lisa Green for technical help and discussions, Adam Aragon from the New Mexico Department of Health for providing samples. This project has been funded with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services , under grant AI067380 (GE) and contracts HHSN272200900018C (Broad Inst.) and HHSN272200900006C (Broad Inst.) from the U.S. NIH . KP was supported by National Research Service Award Institutional Training Grant 5T32-AI07538-13 .
PY - 2012/5/25
Y1 - 2012/5/25
N2 - 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.
AB - 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.
KW - Defective interfering particles
KW - Genetic variation
KW - West Nile virus
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U2 - 10.1016/j.virol.2012.01.028
DO - 10.1016/j.virol.2012.01.028
M3 - Article
C2 - 22365325
AN - SCOPUS:84862793341
SN - 0042-6822
VL - 427
SP - 10
EP - 17
JO - Virology
JF - Virology
IS - 1
ER -