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Title: Genetic Variability of West Nile Virus in U.S. Blood Donors from the 2012 Epidemic Season

West Nile virus (WNV) is an arbovirus maintained in nature in a bird-mosquito enzootic cycle which can also infect other vertebrates including humans. WNV is now endemic in the United States (U.S.), causing yearly outbreaks that have resulted in an estimated total of 4–5 million human infections. Over 41,700 cases of West Nile disease, including 18,810 neuroinvasive cases and 1,765 deaths, were reported to the CDC between 1999 and 2014. In 2012, the second largest West Nile outbreak in the U.S. was reported, which caused 5,674 cases and 286 deaths. WNV continues to evolve, and three major WNV lineage I genotypes (NY99, WN02, and SW/WN03) have been described in the U.S. since introduction of the virus in 1999. We report here the WNV sequences obtained from 19 human samples acquired during the 2012 U.S. outbreak and our examination of the evolutionary dynamics in WNV isolates sequenced from 1999–2012. Maximum-likelihood and Bayesian methods were used to perform the phylogenetic analyses. Selection pressure analyses were performed with the HyPhy package using the Datamonkey web-server. Using different codon-based and branch-site selection models, we detected a number of codons subjected to positive pressure in WNV genes. Thirteen of the 19 completely sequenced isolates frommore » 10 U.S. states were genetically similar, sharing up to 55 nucleotide mutations and 4 amino acid substitutions when compared with the prototype isolate WN-NY99. Altogether, these analyses showed that following a brief contraction in 2008–2009, WNV genetic divergence in the U.S. continued to increase in 2012, and that closely related variants were found across a broad geographic range of the U.S., coincident with the second-largest WNV outbreak in U.S. history.« less
 [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [4] ;  [5] ;  [1] ;  [6]
  1. Food and Drug Administration (FDA), Silver Springs, MD (United States)
  2. Food and Drug Administration (FDA), Silver Springs, MD (United States); Sanofi Pasteur, Swiftwater, PA (United States)
  3. Food and Drug Administration (FDA), Silver Springs, MD (United States); Virginia Commonwealth Univ., Richmond, VA (United States)
  4. Creative Testing Solutions, Tempe, AZ (United States)
  5. American Red Cross, Gaithersburg, MD (United States)
  6. Florida Gulf Coast Univ., Fort Myers, FL (United States)
Publication Date:
Accepted Manuscript
Journal Name:
PLoS Neglected Tropical Diseases (Online)
Additional Journal Information:
Journal Name: PLoS Neglected Tropical Diseases (Online); Journal Volume: 10; Journal Issue: 5; Journal ID: ISSN 1935-2735
Public Library of Science
Research Org:
Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org:
Country of Publication:
United States
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; West Nile virus; bird genetics; phylogenetic analysis; nucleotide sequencing; phylogeography; sequence alignment; substitution mutation; viral evolution
OSTI Identifier: