Blood‐feeding and immunogenic <i>Aedes aegypti</i> saliva proteins

Wasinpiyamongkol, Ladawan; Patramool, Sirilaksana; Luplertlop, Natthanej; Surasombatpattana, Pornapat; Doucouré, Souleymane; Mouchet, François; Séveno, Martial; Remoué, Franck; Demettre, Edith; Brizard, Jean-Paul; Jouin, Patrick; Biron, David G.; Thomas, Frédéric; Missé, Dorothée

doi:10.1002/pmic.200900626

Cited by 61 publications

(63 citation statements)

References 59 publications

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“…At present, we cannot evaluate the fraction of antibodies made specifically against mosquito saliva components, since it is technically difficult to obtain sufficient salivary secretions to use as antigens in an ELISA (potentially thousands of mosquitoes need to be salivated, at 1 to 2 g/ml of protein per mosquito) (2). It is also unclear if these antibodies to mosquito saliva impact DENV disease, as few studies have addressed this issue, with inconclusive results (35,59).…”

Section: Inoculated Mosquitoes Contain Denv In Salivamentioning

confidence: 99%

Mosquito Bite Delivery of Dengue Virus Enhances Immunogenicity and Pathogenesis in Humanized Mice

Cox

Mota

Sukupolvi-Petty

et al. 2012

J Virol

184

205

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bDengue viruses (DENV) are transmitted to humans by the bite of Aedes aegypti or Aedes albopictus mosquitoes, with millions of infections annually in over 100 countries. The diseases they produce, which occur exclusively in humans, are dengue fever (DF) and dengue hemorrhagic fever (DHF). We previously developed a humanized mouse model of DF in which mice transplanted with human hematopoietic stem cells produced signs of DENV disease after injection with low-passage, wild-type isolates. Using these mice, but now allowing infected A. aegypti to transmit dengue virus during feeding, we observed signs of more severe disease (higher and more sustained viremia, erythema, and thrombocytopenia). Dengue fever (DF) in humans is characterized by fever, myalgia, arthralgia, abdominal pain, rash, low platelet counts (thrombocytopenia), and a viremia that begins 3 to 4 days after infection by mosquito bite. The more severe form of dengue, dengue hemorrhagic fever (DHF), usually presents as a second phase of disease, at the end of the fever stage, but with a sudden onset of plasma leakage that can result in hemoconcentration, pleural effusion, ascites, shock, hepatic failure, and encephalopathy. While this hemodynamic syndrome can resolve in 2 days, complete convalescence can take weeks to months (reviewed in reference 53). Moreover, ϳ5% of DHF patients die, usually from hypotensive shock, due to a delay in the recognition and treatment of the plasma leakage. Dengue virus (DENV)-induced disease has increased markedly due to the global spread of the virus and expansion of its mosquito vectors, and it is now the most important viral illness transmitted by insects (61). However, a clear understanding of the mechanisms leading to DF and DHF has been limited by several factors: (i) inadequate animal models of disease, with most knowledge being derived from clinical studies and in vitro experiments; (ii) the genetic diversity of DENV, with four different antigenic groups or serotypes and with humans potentially infected multiple times; and (iii) the relative risk of severe DENV disease, which is enhanced greatly by secondary infection with a heterologous serotype. The last factor has prompted the development of several models of immunopathogenesis (reviewed in reference 47) that have been difficult to evaluate experimentally, given the absence of reliable immunocompetent-animal models of human disease presenting with clinical signs of DHF after serial infection with wild-type viruses.We sought to produce an animal model of disease that could mimic the natural cycle of mosquito-human transmission with low-passage-number viruses from clinical samples, using human cells as targets of infection within a neutral background of nonsusceptible tissues (mouse) and using the appropriate species of mosquito vector, to evaluate the influence of biting/probing, virus delivery, and saliva proteins on DENV pathogenesis. Using humanized NOD/SCID/interleukin 2 receptor gamma (IL-2R␥)-null (hu-NSG) mice that had previously defined differences in th...

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Section: Inoculated Mosquitoes Contain Denv In Salivamentioning

confidence: 99%

Mosquito Bite Delivery of Dengue Virus Enhances Immunogenicity and Pathogenesis in Humanized Mice

Cox

Mota

Sukupolvi-Petty

et al. 2012

J Virol

184

205

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“…funestus bites [17,24–27], and has been used to evaluate the efficacy of insecticide treated nets against malaria transmission [28]. In regard to Aedes species, the 34kDa salivary protein appears to be antigenic and specific to Aedes genus [29–31]. One peptide (the Nterm-34kDa) from this protein in Aedes aegypti saliva has been recently validated, by several studies, as appropriate candidate biomarker of specific exposure to Aedes bites [32,33].…”

Section: Introductionmentioning

confidence: 99%

Human IgG Antibody Response to Aedes Nterm-34kDa Salivary Peptide, an Epidemiological Tool to Assess Vector Control in Chikungunya and Dengue Transmission Area

et al. 2016

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BackgroundArboviral diseases are an important public health concerns. Vector control remains the sole strategy to fight against these diseases. Because of the important limits of methods currently used to assess human exposure to Aedes mosquito bites, much effort is being devoted to develop new indicators. Recent studies have reported that human antibody (Ab) responses to Aedes aegypti Nterm-34kDa salivary peptide represent a promising biomarker tool to evaluate the human-Aedes contact. The present study aims investigate whether such biomarker could be used for assessing the efficacy of vector control against Aedes.Methodology/Principal findingsSpecific human IgG response to the Nterm-34kDa peptide was assessed from 102 individuals living in urban area of Saint-Denis at La Reunion Island, Indian Ocean, before and after the implementation of vector control against Aedes mosquitoes. IgG response decreased after 2 weeks (P < 0.0001), and remained low for 4 weeks post-intervention (P = 0.0002). The specific IgG decrease was associated with the decline of Aedes mosquito density, as estimated by entomological parameters and closely correlated to vector control implementation and was not associated with the use of individual protection, daily commuting outside of the house, sex and age. Our findings indicate a probable short-term decrease of human exposure to Aedes bites just after vector control implementation.Conclusion/SignificanceResults provided in the present study indicate that IgG Ab response to Aedes aegypti Nterm-34kDa salivary peptide could be a relevant short-time indicator for evaluating the efficacy of vector control interventions against Aedes species.

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“…aegypti salivary glands at the transcriptional level and protein expression level [7, 17–23]. Work has been done to ascribe function to some of these salivary components and investigate their individual effects on vertebrate hemostasis and immune response outside the context of a viral infection [8, 17, 24–31].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, Ae. aegypti saliva has been shown to elicit specific IgG and IgE responses in humans [23, 32]. Recent studies have described the effect that DENV infection has on protein expression in the salivary glands or expectorated saliva and postulates how these changes could be relevant to virus transmission [33, 34].…”

Section: Introductionmentioning

confidence: 99%

Aedes aegypti salivary protein “aegyptin” co-inoculation modulates dengue virus infection in the vertebrate host

et al. 2014

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Dengue virus (DENV) is transmitted in the saliva of the mosquito vector Aedes aegypti during blood meal acquisition. This saliva is composed of numerous proteins with the capacity to disrupt hemostasis or modulate the vertebrate immune response. One such protein, termed “aegyptin,” is an allergen and inhibitor of clot formation, and has been found in decreased abundance in the saliva of DENV-infected mosquitoes. To examine the influence of aegyptin on DENV infection of the vertebrate, we inoculated IRF-3/7 −/− −/− mice with DENV serotype 2 strain 1232 with and without co-inoculation of aegyptin. Mice that received aegyptin exhibited decreased DENV titers in inoculation sites and in circulation, as well as increased concentrations of GM-CSF, IFN-γ, IL-5, and IL-6, at 48 hours post inoculation when compared to mice that received inoculation of DENV alone. These and other data suggest that aegyptin impacts DENV perpetuation via elevated induction of the immune response.

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Blood‐feeding and immunogenic Aedes aegypti saliva proteins

Cited by 61 publications

References 59 publications

Mosquito Bite Delivery of Dengue Virus Enhances Immunogenicity and Pathogenesis in Humanized Mice

Mosquito Bite Delivery of Dengue Virus Enhances Immunogenicity and Pathogenesis in Humanized Mice

Human IgG Antibody Response to Aedes Nterm-34kDa Salivary Peptide, an Epidemiological Tool to Assess Vector Control in Chikungunya and Dengue Transmission Area

Aedes aegypti salivary protein “aegyptin” co-inoculation modulates dengue virus infection in the vertebrate host

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