BackgroundRift 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.ObjectiveUsing 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.MethodsC57BL/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.FindingsAfter 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.InterpretationDifferent routes of infection determine the pattern in which the virus spreads and the organs it targets. Aedes saliva significantly increases the pathogenicity of RVFV.

Rift Valley fever virus (RVFV) continues to cause large outbreaks among humans and domestic animals in Africa. RVFV Clone 13, a naturally attenuated clone, is a promising vaccine which was used during the 2009-2010 outbreak in South Africa and played a key role in the control of the disease. In this work, we infected Aedes aegypti mosquitoes with RVFV Clone 13 and prepared salivary gland extracts (SGE). C57BL/6-NRJ male mice were infected with a mixture of SGE infected by Clone 13 and the ZH548 RVFV strain. With the injection of increasing doses of Clone 13-infected SGE, all mice were protected. Our results suggest Clone 13 infected SGE contain unique antiviral components able to counteract the replication of RVFV when injected into vertebrates.