Immunization of Mice with Recombinant Mosquito Salivary Protein D7 Enhances Mortality from Subsequent West Nile Virus Infection via Mosquito Bite

Reagan, Krystle L.; Machaín-Williams, Carlos; Wang, Tian; Blair, Carol D.

doi:10.1371/journal.pntd.0001935

Cited by 47 publications

(40 citation statements)

References 34 publications

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“…In contrast, sensitization of mice to C. tarsalis saliva has no effect on virus levels or morbidity in our previous studies (15). Immunization of mice with C. tarsalis SGE reduces the rates of morbidity and mortality after WNV infection (28), but vaccination against D7, a prominent mosquito salivary protein, increases the rate of mortality during WNV infection (44). Further work is needed to map the interplay between the host immune response, mosquito saliva, and virus replication.…”

Section: Discussionmentioning

confidence: 85%

Parameters of Mosquito-Enhanced West Nile Virus Infection

Moser

Lim

Styer

et al. 2016

J Virol

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The arthropod-borne West Nile virus (WNV) emerged in New York State in 1999 and quickly spread throughout the United States. Transmission is maintained in an enzootic cycle in which infected mosquitoes transmit the virus to susceptible hosts during probing and feeding. Arthropod-derived components within the viral inoculum are increasingly acknowledged to play a role in infection of vertebrate hosts. We previously showed that Culex tarsalis mosquito saliva and salivary gland extract (SGE) enhance the in vivo replication of WNV. Here, we characterized the effective dose, timing, and proximity of saliva and SGE administration necessary for enhancement of WNV viremia using a mouse model. Mosquito saliva and SGE enhanced viremia in a dose-dependent manner, and a single mosquito bite or as little as 0.01 g of SGE was effective at enhancing viremia, suggesting a potent active salivary factor. Viremia was enhanced when SGE was injected in the same location as virus inoculation from 24 h before virus inoculation through 12 h after virus inoculation. These results were confirmed with mosquito saliva deposited by uninfected mosquitoes. When salivary treatment and virus inoculation were spatially separated, viremia was not enhanced. In summary, the effects of mosquito saliva and SGE were potent, long lasting, and localized, and these studies have implications for virus transmission in nature, where vertebrate hosts are fed upon by both infected and uninfected mosquitoes over time. Furthermore, our model provides a robust system to identify the salivary factor(s) responsible for enhancement of WNV replication. IMPORTANCEMosquito-borne viruses are a significant class of agents causing emerging infectious diseases. WNV has caused over 18,000 cases of neuroinvasive disease in the United States since its emergence. We have shown that Culex tarsalis mosquito saliva and SGE enhance the replication of WNV. We now demonstrate that saliva and SGE have potent, long-lasting, and localized effects. Our model provides a robust system to identify the salivary factor(s) and characterize the mechanism responsible for enhancement of WNV replication. These studies could lead to the identification of novel prophylactic or treatment options useful in limiting the spread of WNV, other mosquito-borne viruses, and the diseases that they cause.

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Section: Discussionmentioning

confidence: 85%

Parameters of Mosquito-Enhanced West Nile Virus Infection

Moser

Lim

Styer

et al. 2016

J Virol

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“…In some cases, co-injection of virus and saliva potentiates viral infection of the vertebrate [14], [15], [16], [17]. In other cases, pre-exposure to saliva generates enhances mortality from subsequent viral infection via mosquito bite [18]. A longer viremia was observed in deer and chipmunks infected by mosquito bite containing La Crosse virus, another member of the Bunyaviridae family, compared to syringe injection [19].…”

Section: Introductionmentioning

confidence: 99%

Aedes Mosquito Saliva Modulates Rift Valley Fever Virus Pathogenicity

et al. 2013

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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.

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“…This is particularly well documented for insect-borne viruses such as DV, WNV and the vesicular stomatitis virus (VSV), an arbovirus from the Rhabdoviridae family. 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].…”

Section: Release Of Viruses Into the Host Dermis By Infected Arthropodsmentioning

confidence: 99%

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

Léger

Lozach

2015

Future Virol.

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The Bunyaviridae constitute a large family of animal RNA viruses distributed worldwide, most members of which are transmitted to vertebrate hosts by arthropods and can cause severe pathologies in humans and livestock. With an increasing number of outbreaks, arthropod-borne bunyaviruses (arbo-bunyaviruses) present a global threat to public health and agricultural productivity. Yet transmission, tropism, receptors and cell entry remain poorly characterized. The focus of this review is on the initial infection of mammalian hosts by arbo-bunyaviruses from cellular and molecular perspectives, with particular attention to the human host. We address current knowledge and advances regarding the identity of the first-target cells and the subsequent processes of entry and penetration into the cytosol. Aspects of the vector-to-host switch that influence the early steps of cell infection in mammalian skin, where incoming particles are introduced by infected arthropods, are also highlighted and discussed.

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Immunization of Mice with Recombinant Mosquito Salivary Protein D7 Enhances Mortality from Subsequent West Nile Virus Infection via Mosquito Bite

Cited by 47 publications

References 34 publications

Parameters of Mosquito-Enhanced West Nile Virus Infection

Parameters of Mosquito-Enhanced West Nile Virus Infection

Aedes Mosquito Saliva Modulates Rift Valley Fever Virus Pathogenicity

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

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