Aedes Mosquito Saliva Modulates Rift Valley Fever Virus Pathogenicity

Abstract

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.

Parameters of Mosquito-Enhanced West Nile Virus Infection

“…We published evidence of this dilution in previous studies, which showed that the amount of WNV in artificially collected mosquito saliva is 100-fold lower than the amount of virus inoculated by a mosquito into a live host (19). For these reasons, artificially collected mosquito saliva is infrequently used for in vivo studies, and SGE has been used as a substitute for mosquito saliva in numerous experimental systems (11,16,20,(27)(28)(29)(30)(31)(32)(33)(34)(35). We thus used SGE, which contains secreted salivary factors representative of those obtained by both blood and sugar feeding and which can be produced in sufficient quantities with minimal manipulations that could reduce or eliminate functional activity.…”

“…Deer and chipmunks infected with La Crosse virus by infected Aedes mosquitoes have higher levels of viremia than animals inoculated with virus by needle (10). Mice inoculated with Rift Valley Fever virus and salivary gland extract (SGE) or with Rift Valley Fever virus by infected Aedes aegypti mosquitoes have increased levels of virus in the blood, liver, and brain and enhanced mortality (11). Mice inoculated with dengue virus (DENV) in areas of A. aegypti probing (12,13) or by DENVinfected A. aegypti mosquitoes (13) have higher levels of viremia than mice inoculated by needle.…”

Rift Valley fever virus: strategies for maintenance, survival and vertical transmission in mosquitoes

“…Using in vitro saliva collections it is calculated that mosquitoes inject around 50 p.f.u. ml À1 RVFV with each bite [48,49] although analysis of West Nile virus (WNV; Flavivirus), suggests these methods underestimate titres and vary between species [50].…”

Bunyaviruses: From Transmission by Arthropods to Virus Entry into the Mammalian Host First-Target Cells

“…Infection by these arboviruses through mosquito saliva results in an increase in virus transmission, host susceptibility, viremia, disease progression and mortality [136][137][138][139][140][141][142][143][144]. In the case of arbo-bunyaviruses, the infection of mice is potentiated by the co-injection of mosquito saliva with RVFV or Cache Valley virus, an orthobunyavirus [145,146]. Similarly, co-injection with LACV potentiates infection of white-tailed deer and chipmunks [147].…”