title: Prior exposure to uninfected mosquitoes enhances mortality in naturally-transmitted West Nile virus infection.
abstract: BACKGROUND
  The global emergence of West Nile virus (WNV) has highlighted the importance of mosquito-borne viruses. These are inoculated in vector saliva into the vertebrate skin and circulatory system. Arthropod-borne (arbo)viruses such as WNV are transmitted to vertebrates as an infectious mosquito probes the skin for blood, depositing the virus and saliva into the skin and circulation. Growing evidence has demonstrated that arthropod, and recently mosquito, saliva can have a profound effect on pathogen transmission efficiency, pathogenesis, and disease course. A potentially important aspect of natural infections that has been ignored is that in nature vertebrates are typically exposed to the feeding of uninfected mosquitoes prior to the mosquito that transmits WNV. The possibility that pre-exposure to mosquito saliva might modulate WNV infection was explored.
  
  
  RESULTS
  Here we report that sensitization to mosquito saliva exacerbates viral infection. Prior exposure of mice to mosquito feeding resulted in increased mortality following WNV infection. This aggravated disease course was associated with enhanced early viral replication, increased interleukin-10 expression, and elevated influx of WNV-susceptible cell types to the inoculation site. This exacerbated disease course was mimicked by passive transfer of mosquito-sensitized serum.
  
  
  CONCLUSIONS
  This is the first report that sensitization to arthropod saliva can exacerbate arthropod-borne infection, contrary to previous studies with parasite and bacteria infections. This research suggests that in addition to the seroreactivity of the host to virus, it is important to take into account the immune response to vector feeding.
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Schneider
authors.forename: Charles E
authors.initials: CE
authors.lastname: McGee
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jordan
authors.forename: Heather L
authors.initials: HL
authors.lastname: Stevenson
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.forename: Stephen
authors.initials: S
authors.lastname: Higgs
mesh_terms: D000330:Aedes / Q000821:virology*; D000818:Animals; D007303:Insect Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D014901:West Nile Fever / Q000401:mortality / Q000635:transmission*