title: The evolution of virulence of West Nile virus in a mosquito vector: implications for arbovirus adaptation and evolution.
abstract: BACKGROUND
  Virulence is often coupled with replicative fitness of viruses in vertebrate systems, yet the relationship between virulence and fitness of arthropod-borne viruses (arboviruses) in invertebrates has not been evaluated. Although the interactions between vector-borne pathogens and their invertebrate hosts have been characterized as being largely benign, some costs of arbovirus exposure have been identified for mosquitoes. The extent to which these costs may be strain-specific and the subsequent consequences of these interactions on vector and virus evolution has not been adequately explored.
  
  
  RESULTS
  Using West Nile virus (WNV) and Culex pipiens mosquitoes, we tested the hypothesis that intrahost fitness is correlated with virulence in mosquitoes by evaluating life history traits following exposure to either non-infectious bloodmeals or bloodmeals containing wildtype (WNV WT) or the high fitness, mosquito-adapted strain, WNV MP20 derived from WNV WT. Our results demonstrate strain-specific effects on mosquito survival, fecundity, and blood feeding behavior. Specifically, both resistance to and infection with WNV MP20, but not WNV WT, decreased survival of Cx. pipiens and altered fecundity and bloodfeeding such that early egg output was enhanced at a later cost.
  
  
  CONCLUSIONS
  As predicted by the trade-off hypothesis of virulence, costs of infection with WNV MP20 in terms of survival were directly correlated to viral load, yet resistance to infection with this virulent strain was equally costly. Taken together, these results demonstrate that WNV MP20 infection decreases the transmission potential of Cx. pipiens populations despite the increased intrahost fitness of this strain, indicating that a virulence-transmission trade-off in invertebrates could contribute significantly to the adaptive and evolutionary constraint of arboviruses.
authors.affiliation: Wadsworth Center, Arbovirus laboratory, New York State Department of Health, 5668 State Farm Road, Slingerlands, NY 12159, USA. aciota@wadsworth.org
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Ciota
authors.forename: Dylan J
authors.initials: DJ
authors.lastname: Ehrbar
authors.forename: Amy C
authors.initials: AC
authors.lastname: Matacchiero
authors.forename: Greta A
authors.initials: GA
authors.lastname: Van Slyke
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kramer
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003465:Culex / Q000235:genetics* / Q000254:growth & development / Q000821:virology*; D005260:Female; D056084:Genetic Fitness; D054884:Host-Pathogen Interactions; D007303:Insect Vectors / Q000235:genetics / Q000254:growth & development / Q000821:virology; D008297:Male; D014774:Virulence; D014902:West Nile virus / Q000235:genetics* / Q000472:pathogenicity*