Mosquito Saliva Causes Enhancement of West Nile Virus Infection in Mice

Abstract

West Nile virus (WNV) is transmitted to vertebrate hosts primarily by infected Culex mosquitoes. Transmission of arboviruses by the bite of infected mosquitoes can potentiate infection in hosts compared to viral infection by needle inoculation. Here we examined the effect of mosquito transmission on WNV infection and systematically investigated multiple factors that differ between mosquito infection and needle inoculation of WNV. We found that mice infected with WNV through the bite of a single infected Culex tarsalis mosquito exhibited 5-to 10-fold-higher viremia and tissue titers at 24 and 48 h postinoculation and faster neuroinvasion than mice given a median mosquito-inoculated dose of WNV (10 5 PFU) by needle. Mosquito-induced enhancement was not due to differences in inoculation location, because additional intravenous inoculation of WNV did not enhance viremia or tissue titers. Inoculation of WNV into a location where uninfected mosquitoes had fed resulted in enhanced viremia and tissue titers in mice similar to those in mice infected by a single infected mosquito bite, suggesting that differences in where virus is deposited in the skin and in the virus particle itself were not responsible for the enhanced early infection in mosquito-infected mice. In addition, inoculation of mice with WNV mixed with salivary gland extract (SGE) led to higher viremia, demonstrating that mosquito saliva is the major cause of mosquito-induced enhancement. Enhanced viremia was not observed when SGE was inoculated at a distal site, suggesting that SGE enhances WNV replication by exerting a local effect. Furthermore, enhancement of WNV infection still occurred in mice with antibodies against mosquito saliva. In conclusion, saliva from C. tarsalis is responsible for enhancement of early WNV infection in vertebrate hosts.

EXPERIMENTAL SUSCEPTIBILITY OF WOOD DUCKS (AIX SPONSA) FOR WEST NILE VIRUS

“…However, the viremia developing in mallards was two logs higher than peak viremia in either Wood Ducks or Aigamo Ducks and may have been due to greater susceptibility of mallards to WNV or to enhancement of WNV infection by mosquito saliva, which has been reported in experimentally infected mice (Schneider et al 2007;Styer et al 2011) and chickens (Styer et al 2006). The proportion of Wood Ducks that shed WNV orally is similar to the range of oral shedding of WNV in Aigamo Ducks; however, Aigamo Ducks shed 1-2 logs more WNV.…”

The contribution of rodent models to the pathological assessment of flaviviral infections of the central nervous system

“…Studies comparing subcutaneous inoculation and mosquito transmission of WNV have demonstrated that mosquito saliva can promote the generation of higher viremia early in infection in mice and newly hatched birds, reduce the time taken for the virus to enter the CNS, and elicit higher mortality rates [149,166,167]. Mosquito saliva has been shown to modulate immune cell infiltration at the site of inoculation and reduce the expression of Th1 cytokines and TLR3 [150,174].…”

“…Since capillary-feeding mosquitoes discharge virus-laden saliva into the dermis during probing as well as into the blood during feeding, most studies utilize subcutaneous injection to experimentally mimic the natural route of infection. Subcutaneous co-inoculation of virus with mosquito saliva has also been employed by some groups to imitate natural infection [168].…”

Venom allergen 5is Associated With Deltamethrin Resistance inCulex pipiens pallens(Diptera: Culicidae)

“…Mosquitoes are important vectors of numerous infectious diseases of humans, including malaria (Mitri and Vernick 2012), dengue fever (Jeffery et al 2009), yellow fever (Barrett and Higgs 2007), West Nile fever (Styer et al 2011), encephalitis, and filariasis (Gambhir andMichael 2008, Smith et al 2008). The chemical control of mosquitoes, via the use of insecticides, is the primary means of managing the spread of these diseases, as it is simple, rapid, and economical , Mahande et al 2012.…”