title: Aedes mosquito saliva modulates Rift Valley fever virus pathogenicity.
abstract: BACKGROUND
  Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. Mosquito saliva contains compounds that counteract the hemostatic, inflammatory, and immune responses of the host. Modulation of these defensive responses may facilitate virus infection. Indeed, Aedes mosquito saliva played a crucial role in the vector's capacity to effectively transfer arboviruses such as the Cache Valley and West Nile viruses. The role of mosquito saliva in the transmission of Rift Valley fever virus (RVFV) has not been investigated.
  
  
  OBJECTIVE
  Using a murine model, we explored the potential for mosquitoes to impact the course of RVF disease by determining whether differences in pathogenesis occurred in the presence or absence of mosquito saliva and salivary gland extract.
  
  
  METHODS
  C57BL/6NRJ male mice were infected with the ZH548 strain of RVFV via intraperitoneal or intradermal route, or via bites from RVFV-exposed mosquitoes. The virus titers in mosquitoes and mouse organs were determined by plaque assays.
  
  
  RESULTS
  After intraperitoneal injection, RVFV infection primarily resulted in liver damage. In contrast, RVFV infection via intradermal injection caused both liver and neurological symptoms and this route best mimicked the natural infection by mosquitoes. Co-injections of RVFV with salivary gland extract or saliva via intradermal route increased the mortality rates of mice, as well as the virus titers measured in several organs and in the blood. Furthermore, the blood cell counts of infected mice were altered compared to those of uninfected mice.
  
  
  CONCLUSIONS
  Different routes of infection determine the pattern in which the virus spreads and the organs it targets. Aedes saliva significantly increases the pathogenicity of RVFV.
authors.affiliation: Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Le Coupanec
authors.forename: Divya
authors.initials: D
authors.lastname: Babin
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.forename: Grégory
authors.initials: G
authors.lastname: Jouvion
authors.forename: Patrick
authors.initials: P
authors.lastname: Ave
authors.forename: Dorothee
authors.initials: D
authors.lastname: Misse
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouloy
authors.forename: Valerie
authors.initials: V
authors.lastname: Choumet
mesh_terms: D000330:Aedes / Q000821:virology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012295:Rift Valley Fever / Q000635:transmission* / Q000821:virology*; D012296:Rift Valley fever virus / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity*; D012463:Saliva / Q000821:virology; D019562:Viral Load