Publications by authors named "Valérie Choumet"

41 Publications

CYP450 core involvement in multiple resistance strains of Aedes aegypti from French Guiana highlighted by proteomics, molecular and biochemical studies.

PLoS One 2021 11;16(1):e0243992. Epub 2021 Jan 11.

Unité d'Entomologie Médicale, Institut Pasteur de la Guyane, Cayenne, French Guiana, France.

Insecticide resistance is a worldwide threat for vector control around the world, and Aedes aegypti, the main vector of several arboviruses, is a particular concern. To better understand the mechanisms of resistance, four isofemale strains originally from French Guiana were isolated and analysed using combined approaches. The activity of detoxification enzymes involved in insecticide resistance was assayed, and mutations located at positions 1016 and 1534 of the sodium voltage-gated channel gene, which have been associated with pyrethroid resistance in Aedes aegypti populations in Latin America, were monitored. Resistance to other insecticide families (organophosphates and carbamates) was evaluated. A large-scale proteomic analysis was performed to identify proteins involved in insecticide resistance. Our results revealed a metabolic resistance and resistance associated with a mutation of the sodium voltage-gated channel gene at position 1016. Metabolic resistance was mediated through an increase of esterase activity in most strains but also through the shifts in the abundance of several cytochrome P450 (CYP450s). Overall, resistance to deltamethrin was linked in the isofemale strains to resistance to other class of insecticides, suggesting that cross- and multiple resistance occur through selection of mechanisms of metabolic resistance. These results give some insights into resistance to deltamethrin and into multiple resistance phenomena in populations of Ae. aegypti.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243992PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799788PMC
April 2021

Mayaro Virus Pathogenesis and Transmission Mechanisms.

Pathogens 2020 Sep 8;9(9). Epub 2020 Sep 8.

MIVEGEC, IRD, Univ. Montpellier, CNRS, 34394 Montpellier, France.

Mayaro virus (MAYV), isolated for the first time in Trinidad and Tobago, has captured the attention of public health authorities worldwide following recent outbreaks in the Americas. It has a propensity to be exported outside its original geographical range, because of the vast distribution of its vectors. Moreover, most of the world population is immunologically naïve with respect to infection with MAYV which makes this virus a true threat. The recent invasion of several countries by underscores the risk of potential urban transmission of MAYV in both tropical and temperate regions. In humans, the clinical manifestations of MAYV disease range from mild fever, rash, and joint pain to arthralgia. In the absence of a licensed vaccine and clinically proven therapeutics against Mayaro fever, prevention focuses mainly on household mosquito control. However, as demonstrated for other arboviruses, mosquito control is rather inefficient for outbreak management and alternative approaches to contain the spread of MAYV are therefore necessary. Despite its strong epidemic potential, little is currently known about MAYV. This review addresses various aspects of MAYV, including its epidemiology, vector biology, mode of transmission, and clinical complications, as well as the latest developments in MAYV diagnosis.
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http://dx.doi.org/10.3390/pathogens9090738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558846PMC
September 2020

Differentiation-dependent susceptibility of human muscle cells to Zika virus infection.

PLoS Negl Trop Dis 2020 08 20;14(8):e0008282. Epub 2020 Aug 20.

Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Département de virologie, Institut Pasteur, Paris, France.

Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection, suggesting a differentiation-dependent susceptibility. Infection was accompanied by a caspase-independent cytopathic effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was performed 24h and 48h post-infection in cells infected with two different isolates. Proteome changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, and differentiation-dependent restriction of infection from myoblasts to myotubes. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences in ZIKV infection pathogenesis.
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http://dx.doi.org/10.1371/journal.pntd.0008282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508361PMC
August 2020

Interrupted Blood Feeding in Ticks: Causes and Consequences.

Microorganisms 2020 Jun 16;8(6). Epub 2020 Jun 16.

Ceva Santé Animale, 10 Avenue de la Ballastière, 33500, Libourne, France.

Ticks are obligate hematophagous arthropods and act as vectors for a great variety of pathogens, including viruses, bacteria, protozoa, and helminths. Some tick-borne viruses, such as Powassan virus and tick-borne encephalitis virus, are transmissible within 15-60 min after tick attachment. However, a minimum of 3-24 h of tick attachment is necessary to effectively transmit bacterial agents such as spp., spp., and spp. to a new host. Longer transmission periods were reported for spp. and protozoans such as spp., which require a minimum duration of 24-48 h of tick attachment for maturation and migration of the pathogen. Laboratory observations indicate that the probability of transmission of tick-borne pathogens increases with the duration an infected tick is allowed to remain attached to the host. However, the transmission time may be shortened when partially fed infected ticks detach from their initial host and reattach to a new host, on which they complete their engorgement. For example, early transmission of tick-borne pathogens (e.g., , , and ) and a significantly shorter transmission time were demonstrated in laboratory experiments by interrupted blood feeding. The relevance of such situations under field conditions remains poorly documented. In this review, we explore parameters of, and causes leading to, spontaneous interrupted feeding in nature, as well as the effects of this behavior on the minimum time required for transmission of tick-borne pathogens.
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http://dx.doi.org/10.3390/microorganisms8060910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355616PMC
June 2020

Arboviruses and Muscle Disorders: From Disease to Cell Biology.

Viruses 2020 06 5;12(6). Epub 2020 Jun 5.

Unit of Epidemiology and Physiopathology of Oncogenic Viruses, Institut Pasteur, 75015 Paris, France.

Infections due to arboviruses (arthropod-borne viruses) have dramatically increased worldwide during the last few years. In humans, symptoms associated with acute infection of most arboviruses are often described as "dengue-like syndrome", including fever, rash, conjunctivitis, arthralgia, and muscular symptoms such as myalgia, myositis, or rhabdomyolysis. In some cases, muscular symptoms may persist over months, especially following flavivirus and alphavirus infections. However, in humans the cellular targets of infection in muscle have been rarely identified. Animal models provide insights to elucidate pathological mechanisms through studying viral tropism, viral-induced inflammation, or potential viral persistence in the muscle compartment. The tropism of arboviruses for muscle cells as well as the viral-induced cytopathic effect and cellular alterations can be confirmed in vitro using cellular models. This review describes the link between muscle alterations and arbovirus infection, and the underlying mechanisms.
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http://dx.doi.org/10.3390/v12060616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354517PMC
June 2020

Comparison of a human neuronal model proteome upon Japanese encephalitis or West Nile Virus infection and potential role of mosquito saliva in neuropathogenesis.

PLoS One 2020 6;15(5):e0232585. Epub 2020 May 6.

Institut Pasteur, Environment and Infectious Risks Unit, Arbovirus Group, Paris, France.

Neurotropic flavivirus Japanese encephalitis virus (JEV) and West Nile virus (WNV) are amongst the leading causes of encephalitis. Using label-free quantitative proteomics, we identified proteins differentially expressed upon JEV (gp-3, RP9) or WNV (IS98) infection of human neuroblastoma cells. Data are available via ProteomeXchange with identifier PXD016805. Both viruses were associated with the up-regulation of immune response (IFIT1/3/5, ISG15, OAS, STAT1, IRF9) and the down-regulation of SSBP2 and PAM, involved in gene expression and in neuropeptide amidation respectively. Proteins associated to membranes, involved in extracellular matrix organization and collagen metabolism represented major clusters down-regulated by JEV and WNV. Moreover, transcription regulation and mRNA processing clusters were also heavily regulated by both viruses. The proteome of neuroblastoma cells infected by JEV or WNV was significantly modulated in the presence of mosquito saliva, but distinct patterns were associated to each virus. Mosquito saliva favored modulation of proteins associated with gene regulation in JEV infected neuroblastoma cells while modulation of proteins associated with protein maturation, signal transduction and ion transporters was found in WNV infected neuroblastoma cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232585PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202638PMC
July 2020

Midgut barriers prevent the replication and dissemination of the yellow fever vaccine in Aedes aegypti.

PLoS Negl Trop Dis 2019 08 14;13(8):e0007299. Epub 2019 Aug 14.

Viral Genomics and Vaccination Unit, Institut Pasteur, UMR3569 CNRS, Paris, France.

Background: To be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have to cross several barriers in the mosquito body, including the midgut infection and escape barriers. Yellow fever virus (YFV) belongs to the genus Flavivirus, which includes human viruses transmitted by Aedes mosquitoes, such as dengue and Zika viruses. The live-attenuated YFV-17D vaccine has been used safely and efficiently on a large scale since the end of World War II. Early studies have shown, using viral titration from salivary glands of infected mosquitoes, that YFV-17D can infect Aedes aegypti midgut, but does not disseminate to other tissues.

Methodology/principal Findings: Here, we re-visited this issue using a panel of techniques, such as RT-qPCR, Western blot, immunofluorescence and titration assays. We showed that YFV-17D replication was not efficient in Aedes aegypti midgut, as compared to the clinical isolate YFV-Dakar. Viruses that replicated in the midgut failed to disseminate to secondary organs. When injected into the thorax of mosquitoes, viruses succeeded in replicating into midgut-associated tissues, suggesting that, during natural infection, the block for YFV-17D replication occurs at the basal membrane of the midgut.

Conclusions/significance: The two barriers associated with Ae. aegypti midgut prevent YFV-17D replication. Our study contributes to our basic understanding of vector-pathogen interactions and may also aid in the development of non-transmissible live virus vaccines.
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http://dx.doi.org/10.1371/journal.pntd.0007299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709925PMC
August 2019

Bioluminescent Ross River Virus Allows Live Monitoring of Acute and Long-Term Alphaviral Infection by In Vivo Imaging.

Viruses 2019 06 27;11(7). Epub 2019 Jun 27.

Arbovirus group, Environment and Infectious Risks unit, Pasteur Institute, 75015 Paris, France.

Arboviruses like chikungunya and Ross River (RRV) are responsible for massive outbreaks of viral polyarthritis. There is no effective treatment or vaccine available against these viruses that induce prolonged and disabling arthritis. To explore the physiopathological mechanisms of alphaviral arthritis, we engineered a recombinant RRV expressing a NanoLuc reporter (RRV-NLuc), which exhibited high stability, near native replication kinetics and allowed real time monitoring of viral spread in an albino mouse strain. During the acute phase of the disease, we observed a high bioluminescent signal reflecting viral replication and dissemination in the infected mice. Using Bindarit, an anti-inflammatory drug that inhibits monocyte recruitment, we observed a reduction in viral dissemination demonstrating the important role of monocytes in the propagation of the virus and the adaptation of this model to the evaluation of treatment strategies. After resolution of the acute symptoms, we observed an increase in the bioluminescent signal in mice subjected to an immunosuppressive treatment 30 days post infection, thus showing active in vivo replication of remnant virus. We show here that this novel reporter virus is suitable to study the alphaviral disease up to the chronic phase, opening new perspectives for the evaluation of therapeutic interventions.
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http://dx.doi.org/10.3390/v11070584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669695PMC
June 2019

Infection Kinetics and Tropism of sensu lato in Mouse After Natural (via Ticks) or Artificial (Needle) Infection Depends on the Bacterial Strain.

Front Microbiol 2018 31;9:1722. Epub 2018 Jul 31.

CNR des Borrelia, Institut Pasteur, Paris, France.

sl is a complex of pathogen bacteria transmitted to the host by ticks. European ticks transmit different species, pathogenic to human. Bacteria are principally present in unfed tick midgut, then migrate to salivary glands during blood meal and infect a new host via saliva. In this study, efficiency of transmission in a mouse model of three pathogen species belonging to the sl complex, sensu stricto (B31, N40, and BRE-13), (IBS-5), and (PBi) is examined in order to evaluate infection risk after tick bite. We compared the dissemination of the species in mice after tick bite and needle injection. Location in the ticks and transmission to mice were also determined for the three species by following infection kinetics. After inoculation, we found a significant prevalence in the brain for PBi and BRE-13, in the heart, for PBi, in the skin where B31 was more prevalent than PBi and in the ankle where both B31 and N40 were more present than PBi. After tick bite, statistical analyses showed that BRE-13 was more prevalent than N40 in the brain, in the bladder and in the inguinal lymph node. When dissemination was compared after inoculation and tick bite, we observed heart infection only after tick inoculation of BRE-13, and PBi was only detected after tick bite in the skin. For N40, a higher number of positive organs was found after inoculation compared to tick bite. All European sl strains studied were detected in female salivary glands before blood meal and infected mice within 24 h of tick bite. Moreover, -infected nymphs were able to infect mice as early as 12 h of tick attachment. Our study shows the need to remove ticks as early as possible after attachment. Moreover, tropism varied according to the strain as well as between ticks bite and needle inoculation, confirming the association between some strains and clinical manifestation of Lyme borreliosis, as well as the role played by tick saliva in the efficiency of infection and dissemination in vertebrates.
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http://dx.doi.org/10.3389/fmicb.2018.01722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079464PMC
July 2018

Infection of a French Population of Aedes albopictus and of Aedes aegypti (Paea Strain) with Zika Virus Reveals Low Transmission Rates to These Vectors' Saliva.

Int J Mol Sci 2017 Nov 10;18(11). Epub 2017 Nov 10.

Environment and Infectious Risks Unit, Institut Pasteur, 75015 Paris, France.

Disease caused by the Zika virus (ZIKV) is a public health emergency of international concern. Recent epidemics have emerged in different regions of the world and attest to the ability of the virus to spread wherever its vector, species mosquitoes, can be found. We have compared the transmission of ZIKV by (PAEA strain originating from Tahiti) and by a French population of to better assess their competence and the potential risk of the emergence of ZIKV in Europe. We assessed the transmission of ZIKV by in temperatures similar to those in Southern France during the summer. Our study shows that the extrinsic incubation period of for transmission was shorter than that of . Both vectors were able to transmit ZIKV from 10 to 14 days post-infection. , however, had a longer transmission period than the French population of . Although the salivary glands of both vectors are highly infected, transmission rates of ZIKV to saliva remain relatively low. These observations may suggest that the risk of emergence of ZIKV in Europe could be low.
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http://dx.doi.org/10.3390/ijms18112384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713353PMC
November 2017

Infection of Ixodes ricinus by Borrelia burgdorferi sensu lato in peri-urban forests of France.

PLoS One 2017 28;12(8):e0183543. Epub 2017 Aug 28.

Centre National de Référence des Borrelia, Institut Pasteur, Paris, France.

Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. In Europe, it is transmitted by Ixodes ticks that carry bacteria belonging to the Borrelia burgdorferi sensu lato complex. The objective of this work was to explore eco-epidemiological factors of Lyme borreliosis in peri-urban forests of France (Sénart, Notre-Dame and Rambouillet). We investigated whether the introduction of Tamias sibiricus in Sénart could alter the density of infected ticks. Moreover, the density and tick infection were investigated according to the tree species found in various patches of Sénart forest. For this purpose, ticks were sampled during 3 years. In the Sénart forest, the density of nymph and adult ticks showed no significant difference between 2008, 2009 and 2011. The nymph density varied significantly as a function of the month of collection. Regarding the nymphs, a higher rate of infection and infected density were found in 2009. Plots with chipmunks (C) presented a lower density of both nymphs and adult ticks than plots without chipmunks (NC) did. A higher rate of infection of nymphs with Borrelia was seen in C plots. The prevalence of the various species of Borrelia was also found to vary between C and NC plots with the year of the collect. The presence of chestnut trees positively influenced the density of both nymphs and adults. The infected nymph density showed a significant difference depending on the peri-urban forest studied, Sénart being higher than Rambouillet. The prevalence of Borrelia species also differed between the various forests studied. Concerning the putative role that Tamias sibiricus may play in the transmission of Borrelia, our results suggest that its presence is correlated with a higher rate of infection of questing ticks by Borrelia genospecies and if its population increases, it could play a significant role in the risk of transmission of Lyme borreliosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183543PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573218PMC
October 2017

Co-Infection of Mosquitoes with Chikungunya and Dengue Viruses Reveals Modulation of the Replication of Both Viruses in Midguts and Salivary Glands of Aedes aegypti Mosquitoes.

Int J Mol Sci 2017 Aug 4;18(8). Epub 2017 Aug 4.

Unité Environnement et Risques Infectieux, Institut Pasteur, 75015 Paris, France.

Arthropod-borne virus (arbovirus) infections cause several emerging and resurgent infectious diseases in humans and animals. Chikungunya-affected areas often overlap with dengue-endemic areas. Concurrent dengue virus (DENV) and chikungunya virus (CHIKV) infections have been detected in travelers returning from regions of endemicity. CHIKV and DENV co-infected have also been collected in the vicinity of co-infected human cases, emphasizing the need to study co-infections in mosquitoes. We thus aimed to study the pathogen-pathogen interaction involved in these co-infections in DENV/CHIKV co-infected mosquitoes. In mono-infections, we detected CHIKV antigens as early as 4 days post-virus exposure in both the midgut (MG) and salivary gland (SG), whereas we detected DENV serotype 2 (DENV-2) antigens from day 5 post-virus exposure in MG and day 10 post-virus exposure in SG. Identical infection rates were observed for singly and co-infected mosquitoes, and facilitation of the replication of both viruses at various times post-viral exposure. We observed a higher replication for DENV-2 in SG of co-infected mosquitoes. We showed that mixed CHIKV and DENV infection facilitated viral replication in . The outcome of these mixed infections must be further studied to increase our understanding of pathogen-pathogen interactions in host cells.
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http://dx.doi.org/10.3390/ijms18081708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578098PMC
August 2017

Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking.

Sci Rep 2017 06 9;7(1):3145. Epub 2017 Jun 9.

Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier cedex 5, 34394, France.

Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. Here, we show that compounds interfering with intracellular cholesterol transport have the capacity to inhibit CHIKV replication in human skin fibroblasts, a major viral entry site in the human host. Pretreatment of these cells with the class II cationic amphiphilic compound U18666A, or treatment with the FDA-approved antidepressant drug imipramine resulted in a near total inhibition of viral replication and production at the highest concentration used without any cytotoxic effects. Imipramine was found to affect both the fusion and replication steps of the viral life cycle. The key contribution of cholesterol availability to the CHIKV life cycle was validated further by the use of fibroblasts from Niemann-Pick type C (NPC) patients in which the virus was unable to replicate. Interestingly, imipramine also strongly inhibited the replication of several Flaviviridae family members, including Zika, West Nile and Dengue virus. Together, these data show that this compound is a potential drug candidate for anti-arboviral treatment.
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http://dx.doi.org/10.1038/s41598-017-03316-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466638PMC
June 2017

European Aedes albopictus and Culex pipiens Are Competent Vectors for Japanese Encephalitis Virus.

PLoS Negl Trop Dis 2017 01 13;11(1):e0005294. Epub 2017 Jan 13.

Unité Environnement et Risques Infectieux, Département Infection et Epidémiologie, Institut Pasteur, Paris, France.

Background: Japanese encephalitis virus (JEV) is the causative agent of Japanese encephalitis, the leading cause of viral encephalitis in Asia. JEV transmission cycle involves mosquitoes and vertebrate hosts. The detection of JEV RNA in a pool of Culex pipiens caught in 2010 in Italy raised the concern of a putative emergence of the virus in Europe. We aimed to study the vector competence of European mosquito populations, such as Cx. pipiens and Aedes albopictus for JEV genotypes 3 and 5.

Findings: After oral feeding on an infectious blood meal, mosquitoes were dissected at various times post-virus exposure. We found that the peak for JEV infection and transmission was between 11 and 13 days post-virus exposure. We observed a faster dissemination of both JEV genotypes in Ae. albopictus mosquitoes, when compared with Cx. pipiens mosquitoes. We also dissected salivary glands and collected saliva from infected mosquitoes and showed that Ae. albopictus mosquitoes transmitted JEV earlier than Cx. pipiens. The virus collected from Ae. albopictus and Cx. pipiens saliva was competent at causing pathogenesis in a mouse model for JEV infection. Using this model, we found that mosquito saliva or salivary glands did not enhance the severity of the disease.

Conclusions: In this study, we demonstrated that European populations of Ae. albopictus and Cx. pipiens were efficient vectors for JEV transmission. Susceptible vertebrate species that develop high viremia are an obligatory part of the JEV transmission cycle. This study highlights the need to investigate the susceptibility of potential JEV reservoir hosts in Europe, notably amongst swine populations and local water birds.
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http://dx.doi.org/10.1371/journal.pntd.0005294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5268654PMC
January 2017

The effects of mosquito saliva on dengue virus infectivity in humans.

Curr Opin Virol 2016 12 19;21:139-145. Epub 2016 Oct 19.

Laboratory of MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France. Electronic address:

Arboviruses such as Dengue, Chikungunya, and Zika viruses represent a major public health problem due to globalization and propagation of susceptible vectors worldwide. Arthropod vector-derived salivary factors have the capacity to modulate human cells function by enhancing or suppressing viral replication and, therefore, modify the establishment of local and systemic viral infection. Here, we discuss how mosquito saliva may interfere with Dengue virus (DENV) infection in humans. Identification of saliva factors that enhance infectivity will allow the production of vector-based vaccines and therapeutics that would interfere with viral transmission by targeting arthropod saliva components. Understanding the role of salivary proteins in DENV transmission will provide tools to control not only Dengue but also other arboviral diseases transmitted by the same vectors.
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http://dx.doi.org/10.1016/j.coviro.2016.10.001DOI Listing
December 2016

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.

Lancet 2016 Apr 2;387(10027):1531-1539. Epub 2016 Mar 2.

Service de neurologie, Centre Hospitalier de Polynésie Française, Papeete, Tahiti, Polynésie Française.

Background: Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome.

Methods: In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays.

Findings: 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively).

Interpretation: This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome.

Funding: Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
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http://dx.doi.org/10.1016/S0140-6736(16)00562-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444521PMC
April 2016

Biology of Zika Virus Infection in Human Skin Cells.

J Virol 2015 Sep 17;89(17):8880-96. Epub 2015 Jun 17.

Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM, Montpellier, France

Unlabelled: Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus.

Importance: Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, were all found to be permissive to ZIKV infection. The results also show a major role for the phosphatidylserine receptor AXL as a ZIKV entry receptor and for cellular autophagy in enhancing ZIKV replication in permissive cells. ZIKV replication leads to activation of an antiviral innate immune response and the production of type I interferons in infected cells. Taken together, these results provide the first general insights into the interaction between ZIKV and its mammalian host.
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http://dx.doi.org/10.1128/JVI.00354-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524089PMC
September 2015

Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts.

Infect Genet Evol 2015 Jun 4;32:401-8. Epub 2015 Apr 4.

Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France. Electronic address:

Arboviruses represent an emerging threat to human. They are transmitted to vertebrates by the bite of infected arthropods. Early transmission to vertebrates is initiated by skin puncture and deposition of virus in this organ. However, events at the bite site remain largely unknown. Here, we report that Chikungunya virus (CHIKV) and West Nile virus (WNV), despite belonging to distinct viral families, elicit a common antiviral signature in primary human dermal fibroblasts, attesting for the up regulation of interferon signaling pathways and leading to an increased expression of IFN-β, interleukins and chemokines. Remarkably, CHIKV and WNV enhance IL-1β expression and induce maturation of caspase-1, indicating the capacity of these pathogens to elicit activation of the inflammasome program in resident skin cells. CHIKV and WNV also induce the expression of the inflammasome sensor AIM2 in dermal fibroblasts, whereas inhibition of caspase-1 and AIM2 with siRNA interferes with both CHIKV- and WNV-induced IL-1β production by these cells. Finally, inhibition of the inflammasome via caspase-1 silencing was found to enhance CHIKV replication in dermal fibroblasts. Together, these results indicate that the skin contributes to the pro-inflammatory and anti-viral microenvironment via the activation of the inflammasome in the early stages following infection with arboviruses.
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http://dx.doi.org/10.1016/j.meegid.2015.03.025DOI Listing
June 2015

Infection of Siberian chipmunks (Tamias sibiricus barberi) with Borrelia sp. reveals a low reservoir competence under experimental conditions.

Ticks Tick Borne Dis 2015 Apr 21;6(3):393-400. Epub 2015 Mar 21.

Unité Epidémiologie Animale (UR INRA 346), Centre de recherche INRA de Clermont-Ferrand/Theix, 63122 Saint Genès Champanelle, France. Electronic address:

Reservoir competence is a key parameter in understanding the role of host species in the epidemiology of multi-host-especially vector-borne-pathogens. With this aim in view, we studied the reservoir competence of the Siberian chipmunk (Tamias sibiricus barberi) recently introduced into Europe, for the multi-host tick-borne bacteria, Borrelia burgdorferi sl, the agent of Lyme borreliosis. T. sibiricus were experimentally exposed to bites from Ixodes ricinus ticks infected with Borrelia burgdorferi sensu stricto and Borrelia afzelii, with subsequent assessment of bacteremia and antibody responses. Borrelia was detected in chipmunk blood samples, ear biopsies and organ necropsies, and in nymphs used for xenodiagnosis (at one and six months after the initial chipmunk infection) via both serological and molecular methods. In total, eight out of twelve chipmunks showed evidence of infection by Borrelia sp., either by ELISA or PCR. Five chipmunks developed an immune response against the bacteria one month after infection. Borrelia infection in at least one organ was observed in seven animals at 14, 38, 93 or 178 days post-infection. Xenodiagnosis was positive for one chipmunk at 38 days, but no longer at 178 days post-infection. Four chipmunks remained uninfected, despite similar infection pressures to those observed in the field. Taken together, these results suggest that chipmunks can be infected through Borrelia-infected tick bites, and can transmit Borrelia to nymphs, but do not remain persistently infected.
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http://dx.doi.org/10.1016/j.ttbdis.2015.03.008DOI Listing
April 2015

Role of skin immune cells on the host susceptibility to mosquito-borne viruses.

Virology 2014 Sep 18;464-465:26-32. Epub 2014 Jul 18.

MIVEGEC (IRD 224 CNRS 5290-UM1-UM2) Maladies infectieuses et vecteurs: écologie, génétique, évolution et contrôle, Centre IRD de Montpellier, Montpellier, France. Electronic address:

Due to climate change and the propagation of competent arthropods worldwide, arboviruses have become pathogens of major medical importance. Early transmission to vertebrates is initiated by skin puncture and deposition of virus together with arthropod saliva in the epidermis and dermis. Saliva components have the capacity to modulate skin cell responses by enhancing and/or counteracting initial replication and establishment of systemic viral infection. Here, we review the nature of the cells targeted by arboviruses at the skin level and discuss the type of cellular responses elicited by these pathogens in light of the immunomodulatory properties of arthropod vector-derived salivary factors injected at the inoculation site. Understanding cutaneous arbovirus-host interactions may provide new clues for the design of future therapeutics.
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http://dx.doi.org/10.1016/j.virol.2014.06.023DOI Listing
September 2014

Comparative population genomics of the Borrelia burgdorferi species complex reveals high degree of genetic isolation among species and underscores benefits and constraints to studying intra-specific epidemiological processes.

PLoS One 2014 10;9(4):e94384. Epub 2014 Apr 10.

INRA, UR346 Epidémiologie Animale, Saint Genès Champanelle, France.

Lyme borreliosis, one of the most frequently contracted zoonotic diseases in the Northern Hemisphere, is caused by bacteria belonging to different genetic groups within the Borrelia burgdorferi species complex, which are transmitted by ticks among various wildlife reservoirs, such as small mammals and birds. These features make the Borrelia burgdorferi species complex an attractive biological model that can be used to study the diversification and the epidemiology of endemic bacterial pathogens. We investigated the potential of population genomic approaches to study these processes. Sixty-three strains belonging to three species within the Borrelia burgdorferi complex were isolated from questing ticks in Alsace (France), a region where Lyme disease is highly endemic. We first aimed to characterize the degree of genetic isolation among the species sampled. Phylogenetic and coalescent-based analyses revealed clear delineations: there was a ∼50 fold difference between intra-specific and inter-specific recombination rates. We then investigated whether the population genomic data contained information of epidemiological relevance. In phylogenies inferred using most of the genome, conspecific strains did not cluster in clades. These results raise questions about the relevance of different strategies when investigating pathogen epidemiology. For instance, here, both classical analytic approaches and phylodynamic simulations suggested that population sizes and migration rates were higher in B. garinii populations, which are normally associated with birds, than in B. burgdorferi s.s. populations. The phylogenetic analyses of the infection-related ospC gene and its flanking region provided additional support for this finding. Traces of recombination among the B. burgdorferi s.s. lineages and lineages associated with small mammals were found, suggesting that they shared the same hosts. Altogether, these results provide baseline evidence that can be used to formulate hypotheses regarding the host range of B. burgdorferi lineages based on population genomic data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094384PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993988PMC
December 2014

Clone 13-infected Aedes aegypti salivary components inhibit Rift Valley fever virus pathogenicity.

Microbes Infect 2014 May 13;16(5):439-44. Epub 2014 Feb 13.

Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, 25 rue du Dr Roux, Paris, France; Unité Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, 25 rue du Dr Roux, Paris, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.micinf.2014.01.008DOI Listing
May 2014

Differential expression of Ixodes ricinus salivary gland proteins in the presence of the Borrelia burgdorferi sensu lato complex.

J Proteomics 2014 Jan 2;96:29-43. Epub 2013 Nov 2.

CNR des Borrelia, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex 15, France; Unité Interactions Moléculaires Flavivirus-Hôtes, 25 rue du Dr Roux, 75724 Paris cedex 15, France.

Unlabelled: In Europe, Ixodes ricinus is the main vector of Lyme borreliosis. Their salivary glands play a critical role in the biological success of ticks. To better understand the cross-talk between Borrelia burgdorferi and tick salivary glands, we analyzed protein expression in the salivary glands of I. ricinus adult ticks that were infected by various strains of the B. burgdorferi sl complex. iTRAQ allowed the identification of more than 120 proteins, providing the first proteomic data pertaining to I. ricinus salivary glands. Among these proteins, only 12 were modulated in the presence of various Borrelia strains. Most of them are up-regulated and are involved in cell defense and protein synthesis and processing. Down-regulated proteins are mostly implicated in the cytoskeleton. The DIGE analysis allowed us to identify 35 proteins and showed the down-regulation of 4 proteins. All 15 proteins were not modulated by all strains. Overall, these observations showed that the presence of Borrelia in tick salivary glands is a factor of stress for the protein machinery, and also that some Borrelia strains produce a dysregulation of cytoskeletal proteins. Interestingly, a protein from Borrelia, OspA, was found in infected salivary glands. The consequence of its presence in salivary glands is discussed.

Biological Significance: Lyme borreliosis is still the most prevalent arthropod-borne disease in the temperate regions of the northern hemisphere. The geographical distribution of Lyme borreliosis is expanding, especially towards higher altitudes and latitudes. Human pathogenic spirochetes causing Lyme borreliosis belong to the B. burgdorferi sensu lato complex. They are extracellular pathogens transmitted to humans through the bite of Ixodes spp. ticks. The bioactive molecules present in tick saliva not only promote tick feeding, but also create an advantageous microenvironment at the tick bite site for survival and replication of Borrelia bacteria. Investigation of the tick-host-pathogen interface would provide new strategies to control tick-borne infections. We chose to analyze the interaction of several strains of the B. burgdorferi sensu lato complex with I. ricinus salivary glands. We also investigated the presence of bacterial proteins in salivary glands. For these purposes, we undertook a proteomic study implying the complementary approaches of iTRAQ and DIGE. Our study allowed identifying several salivary markers of infection that were shown to vary according to the strain. Moreover, OspA, a bacterial protein was shown to be expressed in salivary glands and may be implied in the pathogenicity of some Borrelia strains.
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http://dx.doi.org/10.1016/j.jprot.2013.10.033DOI Listing
January 2014

Aedes mosquito saliva modulates Rift Valley fever virus pathogenicity.

PLoS Negl Trop Dis 2013 13;7(6):e2237. Epub 2013 Jun 13.

Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, Paris, France.

Background: Rift 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.

Objective: Using 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.

Methods: C57BL/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.

Findings: After 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.

Interpretation: Different 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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http://dx.doi.org/10.1371/journal.pntd.0002237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681724PMC
December 2013

New markers in Anopheles gambiae salivary glands after Plasmodium berghei infection.

Vector Borne Zoonotic Dis 2013 Feb 5;13(2):119-27. Epub 2013 Jan 5.

Unité de Biochimie et de Biologie Moléculaire des Insectes, Institut Pasteur, Paris Cedex, France.

In malaria, mosquito saliva and salivary glands play central roles in the multi-faceted interactions that occur among the parasite, its vector, and its host. Analyzing the processes involved in the survival and maintenance of the Plasmodium parasite in mosquito organs, and in its transmission into vertebrate hosts, may lead to the identification of new molecular targets for parasite control. We used comparative two-dimensional gel polyacrylamide electrophoresis (2D-PAGE), surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), and high-performance liquid chromatography (HPLC), followed by Edman sequencing, to study saliva and salivary gland samples from Anopheles gambiae mosquitoes infected or not with Plasmodium berghei. Quantitative 2D-PAGE profile analysis showed that the intensities of seven spots were affected by the presence of the parasite in the salivary glands. Most of the proteins identified possessed a signal peptide. SELDI-TOF-MS revealed 32 proteins/peptides whose peak intensities differed between the Plasmodium-infected and non-infected control groups. Quantitative comparison of HPLC profiles of low-molecular-weight components from salivary gland extracts revealed several peptides and proteins with levels that were modulated by parasite infection. The results of these complementary approaches suggest that the infection of female A. gambiae mosquitoes by P. berghei alters the production levels of several salivary gland proteins and peptides, some of which (e.g., protein cE5, B3VDI9_ANOGA, and AGAP008216-PA) are known or predicted to be secreted in saliva and involved in blood feeding.
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http://dx.doi.org/10.1089/vbz.2012.0964DOI Listing
February 2013

Visualizing non infectious and infectious Anopheles gambiae blood feedings in naive and saliva-immunized mice.

PLoS One 2012 13;7(12):e50464. Epub 2012 Dec 13.

Unité de Biochimie et de Biologie Moléculaire des Insectes, Institut Pasteur, Paris, France.

Background: Anopheles gambiae is a major vector of malaria and lymphatic filariasis. The arthropod-host interactions occurring at the skin interface are complex and dynamic. We used a global approach to describe the interaction between the mosquito (infected or uninfected) and the skin of mammals during blood feeding.

Methods: Intravital video microscopy was used to characterize several features during blood feeding. The deposition and movement of Plasmodium berghei sporozoites in the dermis were also observed. We also used histological techniques to analyze the impact of infected and uninfected feedings on the skin cell response in naive mice.

Results: The mouthparts were highly mobile within the skin during the probing phase. Probing time increased with mosquito age, with possible effects on pathogen transmission. Repletion was achieved by capillary feeding. The presence of sporozoites in the salivary glands modified the behavior of the mosquitoes, with infected females tending to probe more than uninfected females (86% versus 44%). A white area around the tip of the proboscis was observed when the mosquitoes fed on blood from the vessels of mice immunized with saliva. Mosquito feedings elicited an acute inflammatory response in naive mice that peaked three hours after the bite. Polynuclear and mast cells were associated with saliva deposits. We describe the first visualization of saliva in the skin by immunohistochemistry (IHC) with antibodies directed against saliva. Both saliva deposits and sporozoites were detected in the skin for up to 18 h after the bite.

Conclusion: This study, in which we visualized the probing and engorgement phases of Anopheles gambiae blood meals, provides precise information about the behavior of the insect as a function of its infection status and the presence or absence of anti-saliva antibodies. It also provides insight into the possible consequences of the inflammatory reaction for blood feeding and pathogen transmission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0050464PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521732PMC
June 2013

Infection by chikungunya virus modulates the expression of several proteins in Aedes aegypti salivary glands.

Parasit Vectors 2012 Nov 15;5:264. Epub 2012 Nov 15.

Unité de Génétique Moléculaire des Bunyavirus, Paris, France.

Background: Arthropod-borne viral infections cause several emerging and resurging infectious diseases. Among the diseases caused by arboviruses, chikungunya is responsible for a high level of severe human disease worldwide. The salivary glands of mosquitoes are the last barrier before pathogen transmission.

Methods: We undertook a proteomic approach to characterize the key virus/vector interactions and host protein modifications that occur in the salivary glands that could be responsible for viral transmission by using quantitative two-dimensional electrophoresis.

Results: We defined the protein modulations in the salivary glands of Aedes aegypti that were triggered 3 and 5 days after an oral infection (3 and 5 DPI) with chikungunya virus (CHIKV). Gel profile comparisons showed that CHIKV at 3 DPI modulated the level of 13 proteins, and at 5 DPI 20 proteins. The amount of 10 putatively secreted proteins was regulated at both time points. These proteins were implicated in blood-feeding or in immunity, but many have no known function. CHIKV also modulated the quantity of proteins involved in several metabolic pathways and in cell signalling.

Conclusion: Our study constitutes the first analysis of the protein response of Aedes aegypti salivary glands infected with CHIKV. We found that the differentially regulated proteins in response to viral infection include structural proteins and enzymes for several metabolic pathways. Some may favour virus survival, replication and transmission, suggesting a subversion of the insect cell metabolism by arboviruses. For example, proteins involved in blood-feeding such as the short D7, an adenosine deaminase and inosine-uridine preferring nucleoside hydrolase, may favour virus transmission by exerting an increased anti-inflammatory effect. This would allow the vector to bite without the bite being detected. Other proteins, like the anti-freeze protein, may support vector protection.
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http://dx.doi.org/10.1186/1756-3305-5-264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549772PMC
November 2012

Update on the proteomics of major arthropod vectors of human and animal pathogens.

Proteomics 2012 Dec 12;12(23-24):3510-23. Epub 2012 Nov 12.

Laboratoire MIVEGEC, UMR CNRS 5290/IRD 224/UM1, Montpellier, France.

Vector-borne diseases (VBDs) are defined as infectious diseases of humans and animals caused by pathogenic agents such as viruses, protists, bacteria, and helminths transmitted by the bite of blood-feeding arthropod (BFA) vectors. VBDs represent a major public health threat in endemic areas, generally subtropical zones, and many are considered to be neglected diseases. Genome sequencing of some arthropod vectors as well as modern proteomic and genomic technologies are expanding our knowledge of arthropod-pathogen interactions. This review describes the proteomic approaches that have been used to investigate diverse biological questions about arthropod vectors, including the interplay between vectors and pathogens. Proteomic studies have identified proteins and biochemical pathways that may be involved in molecular crosstalk in BFA-pathogen associations. Future work can build upon this promising start and functional analyses coupled with interactome bioassays will be carried out to investigate the role of candidate peptides and proteins in BFA-human pathogen associations. Dissection of the host-pathogen interactome will be key to understanding the strategies and biochemical pathways used by BFAs to cope with pathogens.
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http://dx.doi.org/10.1002/pmic.201200300DOI Listing
December 2012

Guillain-Barre syndrome: first description of a snake envenomation aetiology.

J Neuroimmunol 2012 Jan 15;242(1-2):72-7. Epub 2011 Dec 15.

Laboratoire d'Immunochimie, Département d'Immunologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Background: Guillain-Barre syndrome (GBS) is considered as an acute, immune-mediated polyradiculoneuropathy with different clinical phenotypes arising after viral or bacterial infections, vaccination or surgery. However, in 40% of GBS patients the aetiology remains unknown. In this manuscript, we report the occurrence of GBS in a patient bitten by a snake (Vipera aspis) for which a cross-reaction was shown between GM2 ganglioside and glycosidic epitopes of venom proteins.

Methods: The venom of the snake implied in the patient's envenomation was collected. Its composition was characterised by ELISA and SELDI-TOF MS. Cross-reactivities between venom proteins and GM2 gangliosides were identified by Western blot after immunoabsorption of patient's serum with increasing amounts of purified GM2. Enzymatic deglycosylation of the venom was performed to determine the specificity of the patient's serum cross-reaction.

Findings: We proved the absence of neurotoxicity of the viper venom. The patient's serum presented specific cross-reactions with several glycosylated venom proteins. After deglycolysation of these proteins, the patient's serum cross-reactivity was abolished. Furthermore, we compared the immune response to venom proteins of sera from two groups of patients. The first group showed IgM reactivity against GM2 ganglioside associated with GBS, and cross-reacted with venom proteins. The second group presented an IgM reactivity against CMV, without neurological disorders, and reacted with neither venom proteins nor gangliosides.

Interpretation: Our study proved the auto-immunological aetiology of GBS in our patient based on molecular mimicry mechanisms between venom proteins and GM2 ganglioside.
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http://dx.doi.org/10.1016/j.jneuroim.2011.11.007DOI Listing
January 2012

Proteomic analysis of an Aedes albopictus cell line infected with Dengue serotypes 1 and 3 viruses.

Parasit Vectors 2011 Jul 18;4:138. Epub 2011 Jul 18.

Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 5290 CNRS/IRD/UM1, Montpellier, France.

Background: Proteomic analysis was performed to identify proteins regulated during infection by Dengue serotypes 1 and 3 in an Aedes albopictus cell line. The potential of these viruses to cause severe disease at primary infection is of interest although few studies have been performed with these two Dengue serotypes.

Results: The most relevant observation of our study is the significant overexpression of proteins involved in the cellular stress response and the glycolysis pathway after 48 hours of infection. Viral infection activates the translation of some host genes, which may result in stress due to responses involving unfolded proteins.

Conclusions: Therefore, the oxidation reduction and glycolytic mechanisms could participate in the antiviral response against Dengue virus. The results of our study should help to improve our knowledge of the virus-mosquito interaction at a cellular level with the aim of designing efficient strategies for the control of Dengue virus.
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http://dx.doi.org/10.1186/1756-3305-4-138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151224PMC
July 2011