Dorothée Missé - Academia.edu (original) (raw)
Papers by Dorothée Missé
Pathogens, 2021
Reported for the first time in 1955 in Malaysia, Tembusu virus (TMUV) remained, for a long time, ... more Reported for the first time in 1955 in Malaysia, Tembusu virus (TMUV) remained, for a long time, in the shadow of flaviviruses with human health importance such as dengue virus or Japanese encephalitis virus. However, since 2010 and the first large epidemic in duck farms in China, the threat of its emergence on a large scale in Asia or even its spillover into the human population is becoming more and more significant. This review aims to report current knowledge on TMUV from viral particle organization to the development of specific vaccines and therapeutics, with a particular focus on host-virus interactions.
Viruses, 2021
Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with... more Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipi...
Pathogens, 2020
Mayaro virus (MAYV), isolated for the first time in Trinidad and Tobago, has captured the attenti... more 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 Aedesalbopictus 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 alternativ...
Journal of Virology, 1998
To evaluate conserved structures of the surface gp120 subunit (SU) of the human immunodeficiency ... more To evaluate conserved structures of the surface gp120 subunit (SU) of the human immunodeficiency virus type 1 (HIV-1) envelope in gp120-cell interactions, we designed and produced an HIV-1 IIIB (HXB2R) gp120 carrying a deletion of amino acids E61 to S85. This sequence corresponds to a highly conserved predicted amphipathic alpha-helical structure located in the gp120 C1 region. The resultant soluble mutant with a deleted alpha helix 1 (gp120 ΔαHX1) exhibited a strong interaction with CXCR4, although CD4 binding was undetectable. The former interaction was specific since it inhibited the binding of the anti-CXCR4 monoclonal antibody (12G5), as well as SDF1α, the natural ligand of CXCR4. Additionally, the mutant gp120 was able to bind to CXCR4+/CD4− cells but not to CXCR4−/CD4− cells. Although efficiently expressed on cell surface, HIV envelope harboring the deleted gp120 ΔαHX1 associated with wild-type transmembrane gp41 was unable to induce cell-to-cell fusion with HeLa CD4+ cells. ...
Viruses, 2019
Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togav... more Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility of Aedes aegypti and Aedes albopictus to infection with MAYV and their innate immune response at an early stage of infection. Aedes albopictus was more susceptible to infection with MAYV than Ae. aegypti. Analysis of transcript levels of twenty immunity-related genes by real-time PCR in the midgut of both mosquitoes infected with MAYV revealed increased expression of several immune genes, including CLIP-domain serine proteases, the anti-microbial peptides defensin A, E, cecropin E, and the virus inducible gene. The regulation of certain genes appeared to be Aedes species-dependent. Infection of Ae. aegypti with MAYV resulted in increased levels of myeloid differentiation2-related lipi...
Scientific reports, Jan 9, 2017
Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present... more 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 replica...
BMC cancer, Apr 12, 2017
Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of ca... more Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction. Lost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways - from functional aspects to evolutionary considerations such as modernity mismatches - by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels. Infectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase ou...
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2017
ZIKA virus (ZIKV) is a newly emerging arbovirus. Since its discovery 60years ago in Uganda, it ha... more ZIKA virus (ZIKV) is a newly emerging arbovirus. Since its discovery 60years ago in Uganda, it has spread throughout the Pacific, Latin America and the Caribbean, emphasizing the capacity of ZIKV to spread to non-endemic regions worldwide. Although infection with ZIKV often leads to mild disease, its recent emergence in the Americas has coincided with an increase in adults developing Guillain-Barré syndrome and neurological complications in new-borns, such as congenital microcephaly. Many questions remain unanswered regarding the complications caused by different primary isolates of ZIKV. Here, we report the permissiveness of primary human astrocytes for two clinically relevant, Asian and African ZIKV strains and show that both isolates strongly induce antiviral immune responses in these cells albeit with markedly different kinetics. This study describes for the first time the specific antiviral gene expression in infected primary human astrocytes, the major glial cells within the c...
The invection relates to the use of IL-22 alone or in combination as biomarker of resistance to i... more The invection relates to the use of IL-22 alone or in combination as biomarker of resistance to infections in humans when added to of one or several agonists of the formyl peptide receptors (FPR) receptors family and formyl peptide receptors-like 1 (FPRL 1). Said biomarker is useful in diagnostics, prophylaxis and therapeutics
The invention provides a method of treating viral haemorrhagic fevers, such as that caused by Den... more The invention provides a method of treating viral haemorrhagic fevers, such as that caused by Dengue virus, which comprises administering a composition comprising a pharmaceutically active amount of a matrix metalloproteinase inhibito
Parasitology, 2016
SUMMARYDespite important differences between infectious diseases and cancers, tumour development ... more SUMMARYDespite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host–parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and...
Evolutionary Applications, 2015
The evolutionary perspective of cancer (which origins and dynamics result from evolutionary proce... more The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights into evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion, it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free-living species appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in patients with cancer, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, Jan 3, 2015
Arboviruses represent an emerging threat to human. They are transmitted to vertebrates by the bit... more 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 signalling 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...
Genetics and Evolution of Infectious Disease, 2011
Dependent on detergents used Marginal No Yes Yes Moderate Cheap 2-DIGE Electrophoresis: IEF PAGE ... more Dependent on detergents used Marginal No Yes Yes Moderate Cheap 2-DIGE Electrophoresis: IEF PAGE Densitometry of Cy3-and Cy5labeled proteins normalize to Cy2 Mass spectrometry (PMF;MS/MS) Dependent on detergents used Moderate (especially with scanning gels) No Yes Yes Moderate Expensive MuDPIT LCÀLC of peptides None Mass spectrometry (MS/MS) Theoretically better than electrophoresis but not systematically examined Moderate, often used with large sample amounts No Yes Yes Rapid Moderate ICATt LC of peptides Through use of heavy and light tags Mass spectrometry (MS/MS) No better than 2-DE Moderate No Yes No Rapid Moderate SELDI-TOF-MS Binding of proteins based on their chemical and physical characteristics Comparison of MS peaks Requires series of samples or coupling to second MS instrument Moderate Marginal to moderate No Yes No Rapid Expensive Protein arrays Antibody-based chips (binding to affinity reagent) Densitometry of binding Binding to particular affinity reagent Unknown Unknown Yes No Yes Rapid Cheap 2-DE: two-dimensional electrophoresis; 2-DIGE: two-dimensional difference in gel electrophoresis; MuDPIT: multidimensional protein identification technology; LC: liquid chromatography; LCÀLC: tandem liquid chromatography; PAGE: polyacrylamide gel electrophoresis; ICAT: isotopecoded affinity tags; SELDI-TOF-MS: spectrum-enhanced laser desorption ionizationÀtime of flightÀmass spectrometry; PMF: peptide mass fingerprint; MS/MS: tandem mass spectrometry.
Trends in Ecology & Evolution, 2009
PROTEOMICS – CLINICAL APPLICATIONS, 2008
PLoS Pathogens, 2011
The ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on cro... more The ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti). Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD) and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598). Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV) and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptidecontaining form of this peptide.
PLoS Neglected Tropical Diseases, 2012
Background: Much effort is being devoted for developing new indicators to evaluate the human expo... more Background: Much effort is being devoted for developing new indicators to evaluate the human exposure to Aedes mosquito bites and the risk of arbovirus transmission. Human antibody (Ab) responses to mosquito salivary components could represent a promising tool for evaluating the human-vector contact. Methodology/Principal findings: To develop a specific biomarker of human exposure to Aedes aegypti bites, we measured IgG Ab response to Ae. aegypti Nterm-34 kDa salivary peptide in exposed children in 7 villages of Southern Benin (West Africa). Results showed that specific IgG response presented high inter-individual heterogeneity between villages. IgG response was associated with rainfall and IgG level increased from dry (low exposure) to rainy (high exposure) seasons. These findings indicate that IgG Ab to Nterm-34 kDa salivary peptide may represent a reliable biomarker to detect variation in human exposure to Ae. aegypti bites. Conclusion/Significance: This preliminary study highlights the potential use of Ab response to this salivary peptide for evaluating human exposure to Ae. aegypti. This biomarker could represent a new promising tool for assessing the risk of arbovirus transmission and for evaluating the efficacy of vector control interventions.
Nature Biotechnology, 2002
The conserved surfaces of the human immunodeficiency virus (HIV)-1 envelope involved in receptor ... more The conserved surfaces of the human immunodeficiency virus (HIV)-1 envelope involved in receptor binding represent potential targets for the development of entry inhibitors and neutralizing antibodies. Using structural information on a CD4-gp120-17b antibody complex, we have designed a 27-amino acid CD4 mimic, CD4M33, that presents optimal interactions with gp120 and binds to viral particles and diverse HIV-1 envelopes with CD4-like affinity. This mini-CD4 inhibits infection of both immortalized and primary cells by HIV-1, including primary patient isolates that are generally resistant to inhibition by soluble CD4. Furthermore, CD4M33 possesses functional properties of CD4, including the ability to unmask conserved neutralization epitopes of gp120 that are cryptic on the unbound glycoprotein. CD4M33 is a prototype of inhibitors of HIV-1 entry and, in complex with envelope proteins, a potential component of vaccine formulations, or a molecular target in phage display technology to develop broad-spectrum neutralizing antibodies.
Pathogens, 2021
Reported for the first time in 1955 in Malaysia, Tembusu virus (TMUV) remained, for a long time, ... more Reported for the first time in 1955 in Malaysia, Tembusu virus (TMUV) remained, for a long time, in the shadow of flaviviruses with human health importance such as dengue virus or Japanese encephalitis virus. However, since 2010 and the first large epidemic in duck farms in China, the threat of its emergence on a large scale in Asia or even its spillover into the human population is becoming more and more significant. This review aims to report current knowledge on TMUV from viral particle organization to the development of specific vaccines and therapeutics, with a particular focus on host-virus interactions.
Viruses, 2021
Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with... more Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipi...
Pathogens, 2020
Mayaro virus (MAYV), isolated for the first time in Trinidad and Tobago, has captured the attenti... more 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 Aedesalbopictus 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 alternativ...
Journal of Virology, 1998
To evaluate conserved structures of the surface gp120 subunit (SU) of the human immunodeficiency ... more To evaluate conserved structures of the surface gp120 subunit (SU) of the human immunodeficiency virus type 1 (HIV-1) envelope in gp120-cell interactions, we designed and produced an HIV-1 IIIB (HXB2R) gp120 carrying a deletion of amino acids E61 to S85. This sequence corresponds to a highly conserved predicted amphipathic alpha-helical structure located in the gp120 C1 region. The resultant soluble mutant with a deleted alpha helix 1 (gp120 ΔαHX1) exhibited a strong interaction with CXCR4, although CD4 binding was undetectable. The former interaction was specific since it inhibited the binding of the anti-CXCR4 monoclonal antibody (12G5), as well as SDF1α, the natural ligand of CXCR4. Additionally, the mutant gp120 was able to bind to CXCR4+/CD4− cells but not to CXCR4−/CD4− cells. Although efficiently expressed on cell surface, HIV envelope harboring the deleted gp120 ΔαHX1 associated with wild-type transmembrane gp41 was unable to induce cell-to-cell fusion with HeLa CD4+ cells. ...
Viruses, 2019
Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togav... more Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility of Aedes aegypti and Aedes albopictus to infection with MAYV and their innate immune response at an early stage of infection. Aedes albopictus was more susceptible to infection with MAYV than Ae. aegypti. Analysis of transcript levels of twenty immunity-related genes by real-time PCR in the midgut of both mosquitoes infected with MAYV revealed increased expression of several immune genes, including CLIP-domain serine proteases, the anti-microbial peptides defensin A, E, cecropin E, and the virus inducible gene. The regulation of certain genes appeared to be Aedes species-dependent. Infection of Ae. aegypti with MAYV resulted in increased levels of myeloid differentiation2-related lipi...
Scientific reports, Jan 9, 2017
Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present... more 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 replica...
BMC cancer, Apr 12, 2017
Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of ca... more Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction. Lost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways - from functional aspects to evolutionary considerations such as modernity mismatches - by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels. Infectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase ou...
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2017
ZIKA virus (ZIKV) is a newly emerging arbovirus. Since its discovery 60years ago in Uganda, it ha... more ZIKA virus (ZIKV) is a newly emerging arbovirus. Since its discovery 60years ago in Uganda, it has spread throughout the Pacific, Latin America and the Caribbean, emphasizing the capacity of ZIKV to spread to non-endemic regions worldwide. Although infection with ZIKV often leads to mild disease, its recent emergence in the Americas has coincided with an increase in adults developing Guillain-Barré syndrome and neurological complications in new-borns, such as congenital microcephaly. Many questions remain unanswered regarding the complications caused by different primary isolates of ZIKV. Here, we report the permissiveness of primary human astrocytes for two clinically relevant, Asian and African ZIKV strains and show that both isolates strongly induce antiviral immune responses in these cells albeit with markedly different kinetics. This study describes for the first time the specific antiviral gene expression in infected primary human astrocytes, the major glial cells within the c...
The invection relates to the use of IL-22 alone or in combination as biomarker of resistance to i... more The invection relates to the use of IL-22 alone or in combination as biomarker of resistance to infections in humans when added to of one or several agonists of the formyl peptide receptors (FPR) receptors family and formyl peptide receptors-like 1 (FPRL 1). Said biomarker is useful in diagnostics, prophylaxis and therapeutics
The invention provides a method of treating viral haemorrhagic fevers, such as that caused by Den... more The invention provides a method of treating viral haemorrhagic fevers, such as that caused by Dengue virus, which comprises administering a composition comprising a pharmaceutically active amount of a matrix metalloproteinase inhibito
Parasitology, 2016
SUMMARYDespite important differences between infectious diseases and cancers, tumour development ... more SUMMARYDespite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host–parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and...
Evolutionary Applications, 2015
The evolutionary perspective of cancer (which origins and dynamics result from evolutionary proce... more The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights into evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion, it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free-living species appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in patients with cancer, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, Jan 3, 2015
Arboviruses represent an emerging threat to human. They are transmitted to vertebrates by the bit... more 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 signalling 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...
Genetics and Evolution of Infectious Disease, 2011
Dependent on detergents used Marginal No Yes Yes Moderate Cheap 2-DIGE Electrophoresis: IEF PAGE ... more Dependent on detergents used Marginal No Yes Yes Moderate Cheap 2-DIGE Electrophoresis: IEF PAGE Densitometry of Cy3-and Cy5labeled proteins normalize to Cy2 Mass spectrometry (PMF;MS/MS) Dependent on detergents used Moderate (especially with scanning gels) No Yes Yes Moderate Expensive MuDPIT LCÀLC of peptides None Mass spectrometry (MS/MS) Theoretically better than electrophoresis but not systematically examined Moderate, often used with large sample amounts No Yes Yes Rapid Moderate ICATt LC of peptides Through use of heavy and light tags Mass spectrometry (MS/MS) No better than 2-DE Moderate No Yes No Rapid Moderate SELDI-TOF-MS Binding of proteins based on their chemical and physical characteristics Comparison of MS peaks Requires series of samples or coupling to second MS instrument Moderate Marginal to moderate No Yes No Rapid Expensive Protein arrays Antibody-based chips (binding to affinity reagent) Densitometry of binding Binding to particular affinity reagent Unknown Unknown Yes No Yes Rapid Cheap 2-DE: two-dimensional electrophoresis; 2-DIGE: two-dimensional difference in gel electrophoresis; MuDPIT: multidimensional protein identification technology; LC: liquid chromatography; LCÀLC: tandem liquid chromatography; PAGE: polyacrylamide gel electrophoresis; ICAT: isotopecoded affinity tags; SELDI-TOF-MS: spectrum-enhanced laser desorption ionizationÀtime of flightÀmass spectrometry; PMF: peptide mass fingerprint; MS/MS: tandem mass spectrometry.
Trends in Ecology & Evolution, 2009
PROTEOMICS – CLINICAL APPLICATIONS, 2008
PLoS Pathogens, 2011
The ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on cro... more The ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti). Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD) and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598). Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV) and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptidecontaining form of this peptide.
PLoS Neglected Tropical Diseases, 2012
Background: Much effort is being devoted for developing new indicators to evaluate the human expo... more Background: Much effort is being devoted for developing new indicators to evaluate the human exposure to Aedes mosquito bites and the risk of arbovirus transmission. Human antibody (Ab) responses to mosquito salivary components could represent a promising tool for evaluating the human-vector contact. Methodology/Principal findings: To develop a specific biomarker of human exposure to Aedes aegypti bites, we measured IgG Ab response to Ae. aegypti Nterm-34 kDa salivary peptide in exposed children in 7 villages of Southern Benin (West Africa). Results showed that specific IgG response presented high inter-individual heterogeneity between villages. IgG response was associated with rainfall and IgG level increased from dry (low exposure) to rainy (high exposure) seasons. These findings indicate that IgG Ab to Nterm-34 kDa salivary peptide may represent a reliable biomarker to detect variation in human exposure to Ae. aegypti bites. Conclusion/Significance: This preliminary study highlights the potential use of Ab response to this salivary peptide for evaluating human exposure to Ae. aegypti. This biomarker could represent a new promising tool for assessing the risk of arbovirus transmission and for evaluating the efficacy of vector control interventions.
Nature Biotechnology, 2002
The conserved surfaces of the human immunodeficiency virus (HIV)-1 envelope involved in receptor ... more The conserved surfaces of the human immunodeficiency virus (HIV)-1 envelope involved in receptor binding represent potential targets for the development of entry inhibitors and neutralizing antibodies. Using structural information on a CD4-gp120-17b antibody complex, we have designed a 27-amino acid CD4 mimic, CD4M33, that presents optimal interactions with gp120 and binds to viral particles and diverse HIV-1 envelopes with CD4-like affinity. This mini-CD4 inhibits infection of both immortalized and primary cells by HIV-1, including primary patient isolates that are generally resistant to inhibition by soluble CD4. Furthermore, CD4M33 possesses functional properties of CD4, including the ability to unmask conserved neutralization epitopes of gp120 that are cryptic on the unbound glycoprotein. CD4M33 is a prototype of inhibitors of HIV-1 entry and, in complex with envelope proteins, a potential component of vaccine formulations, or a molecular target in phage display technology to develop broad-spectrum neutralizing antibodies.