Vinca Lardans - Academia.edu (original) (raw)
Papers by Vinca Lardans
Parasitology Today, 1998
As intermediate hosts, molluscs play a major role in the transmission of schistosomes; they are t... more As intermediate hosts, molluscs play a major role in the transmission of schistosomes; they are the sites of an intense multiplication of parasites. Thus, snail control strategies are considered a priority for the reduction of schistosomiasis transmission. Here, Vinca Lardans and Colette Dissous review the efficacy of environmental management and the use of molluscicides and biological agents to control snail populations. They then describe the development of diagnostic tests, based on the detection of parasite antigens or specific parasite DNA sequences in snail tissues, to detect the early infection of snails. Finally, they discuss progress in studying the molecular basis of susceptibility and resistance phenotypes, and the possible application of the genetic manipulation of molluscs.
Parasitology Research, 1999
We have cloned from Biomphalaria glabrata, the intermediate host of the helminth parasite Schisto... more We have cloned from Biomphalaria glabrata, the intermediate host of the helminth parasite Schistosoma mansoni, a 36-kDa apparent-molecular-mass molecule (BgSel) that shares sequence identity with selectins of the cell-adhesion-molecule superfamily. BgSel exhibited in its C-terminal part a putative C-type lectin domain similar to the selectin lectin domain. Using antibodies to the recombinant BgSel protein, we demonstrated the presence of BgSel in snail hemocytes as well as in the cell line derived from B. glabrata embryos (Bge). Anti-BgSel antibodies specifically recognized a 79-kDa component in Bge-cell-secreted products that was supposed to represent the native form of BgSel, as was confirmed after glycosidase treatment. Lectins are known to be implicated in recognition mechanisms participating in humoral and cellular immunity in molluscs. The possible role of BgSel in the interaction between sporocysts and Bge cells, particularly in the in vitro model of sporocyst development dependent on Bge cell factors, remains to be determined.
Parasitology Research, 1996
... Bge cells can provide good environmental conditions for the development of mother sporocysts ... more ... Bge cells can provide good environmental conditions for the development of mother sporocysts to the daughter form (Yoshino and Laursen 1995). ... The plasmid pDr-luc contained the luci-ferase gene under the control of the heat-shock-respon-sive element from the Drosophila ...
Nucleic Acids Research, 1998
The CCAAT-binding protein NF-Y is involved in the regulation of a variety of eukaryotic genes and... more The CCAAT-binding protein NF-Y is involved in the regulation of a variety of eukaryotic genes and is formed in higher eukaryotes by three subunits NF-YA/ B/C. We have characterized NF-Y of the trematode parasite Schistosoma mansoni and studied the structure and the function of the SMNF-YA subunit. In this work, we present the cloning and sequence analysis of the B subunit of the parasite factor. SMNF-YB contains the conserved HAP-3 homology domain but the remaining part of the protein was found to be highly divergent from all other species. We demonstrated by transfections of GAL4 fusion constructs, that mouse NF-YB does not contain activation domains while the C-terminal part of SMNF-YB has transcriptional activation potential. On the other hand, the N-terminal parts of SMNF-YA and mouse NF-YA were shown to mediate transactivation; the integrity of a large 160 amino acid glutamine-rich domain of NF-YA was required for this function and an adjacent serine-and threonine-rich domain was necessary for full activity in HepG2, but redundant in other cell types. Transactivation domains identified in SMNF-YB are also rich in serine and threonine residues. Our results indicate that serine/threonine-rich sequences from helminth parasites potentiate transcription and that such structures have diverged during evolution within the same transcription factor.
Molecular and Biochemical Parasitology, 2003
Previous studies have suggested that successful development of the parasitic helminth Schistosoma... more Previous studies have suggested that successful development of the parasitic helminth Schistosoma mansoni must be dependent on an adaptative molecular dialogue with its hosts and on the existence of receptors for growth factors and hormones. Attempts to identify a homolog of the insulin receptor (IR) have led us to characterize a new receptor tyrosine kinase (RTK) molecule in S. mansoni. SmRTK-1 is an integral membrane protein with a single membrane-spanning sequence separating an extracellular ligand-binding domain and a cytoplasmic TK domain. Structural and phylogenetic analyses of the kinase domain of SmRTK-1 confirmed its similarity to IR catalytic domains. However, sequence analysis of the extracellular domain of SmRTK-1 revealed similarity with various proteins (such as drug receptors) that share a structure known as the Venus Flytrap (VFT) module. Alignment with other VFT modules for which the structure has been solved was used to generate a 3D model of the putative VFT module of SmRTK-1. Phylogenetic analysis indicated that the SmRTK-1 VFT module was closer to that of the GABA B receptor. Numerous RTK genes recently discovered in vertebrate and invertebrate species code for large families of modular proteins with diverse structures and ligand-binding specificities. SmRTK-1 probably represents a new class of RTK whose function remains to be determined. RTKs are present in all metazoans and associated with the control of metabolism, growth and development. The preferential localization of SmRTK-1 in sporocyst germinal cells and ovocytes could be in favor of its function in schistosome growth and differentiation.
Molecular and Biochemical Parasitology, 1999
Cyclosporin A (CsA) has been found to exert potent anti-parasite activity against a wide range of... more Cyclosporin A (CsA) has been found to exert potent anti-parasite activity against a wide range of protozoan and helminth parasites. In schistosomes, evidence has been accumulated to propose that the drug damages parasites by mechanisms independent of its immunosuppressive properties. Moreover, the absence of correlation between anti-schistosomal properties and inhibition of peptidyl -prolyl cis-trans isomerase activity of cyclophilins (CsA receptors) for various drug analogs, argued against a direct implication of cyclophilins in the lethal effect of CsA. We describe, in S. mansoni, the existence of NF-AT-like transcription factors, a protein family already characterized by its sensitivity to CsA. The observation that CsA treatment of S. mansoni larvae inhibited the expression of the Sm28GST protein and the characterization of a functional NF-AT-like site in the gene encoding this protein, provide new insights in the understanding of the antischistosomal effect of CsA. Our results also support the hypothesis that the regulatory function of NF-AT-like proteins might be responsible for parasite development and survival in the host and open new perspectives in studies of helminth biology.
Journal of General Virology, 1996
Mouse hepatitis viruses (MHV) diversely affect immune responses, depending on the viral strain an... more Mouse hepatitis viruses (MHV) diversely affect immune responses, depending on the viral strain and the mouse genetic background. Here, we studied the effect of MHV-A59 infection on B cell responses of 129/Sv and CBA mice. Our results indicate that in these strains, MHV-A59 induces spleen cell activation that leads to enlargement of the spleen without structural alteration. Infection triggers production by B lymphocytes of large amounts of immunoglobulin G2a, mostly without viral specificity. This polyclonal immunoglobulin production is dependent on the presence of functional T helper cells. This polyclonal B lymphocyte activation induced by MHV-A59 infection can have pathological implications, such as the enhancement of concomitant autoimmune reactions.
Experimental Parasitology, 1998
Lardans, V., Serra, E., Capron, A., and Dissous, C. 1998. Characterpromotion, transformation, and... more Lardans, V., Serra, E., Capron, A., and Dissous, C. 1998. Characterpromotion, transformation, and other signal transduction ization of an intracellular receptor for activated protein kinase C pathways. Activation of PKCs results in phosphorylation of (RACK) from the mollusc Biomphalaria glabrata, the intermediate specific proteins and their selective activity is dependent on host for Schistosoma mansoni. Experimental Parasitology 88, 194-199. specific subcellular targeting that allows their accessibility A receptor for activated protein kinase C (RACK) was characterized from the mollusc Biomphalaria glabrata, the intermediate host for to selected substrates (Liu 1996). the human parasite Schistosoma mansoni. This protein was shown to PKC isoenzymes are among the first signaling proteins possess structural and functional characteristics of other RACK proteins that have been shown to undergo translocation from the from various cells and organisms. Its ability to bind mammalian PKCs cytosol to the particulate fraction upon activation. Translocaalso confirmed the conservation of PKC and RACK interactive domains throughout evolution. Results of immunolocalization indicated the pres-tion of PKCs was first thought to reflect a direct binding of ence of Bg RACK in the cytoplasm of mollusc hemocytes and B. the enzyme to membrane lipids but further data indicated glabrata embryonic (Bge) cells with a more intense staining around that proteins could also anchor activated PKCs at the site of the nucleus. These results are in agreement with the association of translocation (Newton 1995). Many of these PKC-targeting RACK proteins with cytoskeletal elements. ᭧ 1998 Academic Press proteins, essentially implied in cytoskeleton functions, con-
Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 2001
Binding and inhibition studies reveal that the DNA-binding domain (DBD) fragment and the full-len... more Binding and inhibition studies reveal that the DNA-binding domain (DBD) fragment and the full-length molecule of the heat-shock transcription factor of schistosome (SmHSF) differ in DNA sequence recognition. SmHSF does not recognize the ideal HSE consensus sequence (nGAAnnTTCnnGAAn) but recognizes a variant HSE that contains nGTAn instead of nGAAn in the third pentamer. The DBD reacts efficiently with the ideal HSE sequence and with lower affinity with the variant HSE sequence. These findings suggest that elements inside and outside the DBD contribute to the DNA-binding specificity of HSF.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1999
Schistosomes are parasitic helminths with a complex life cycle in human and snail hosts. They exp... more Schistosomes are parasitic helminths with a complex life cycle in human and snail hosts. They express stage-specific genes that conceivably determine distinct properties of the parasite at different developmental stages. Here we report the stage-specific gene SmSPO-1, which is preferentially expressed in sporocysts residing in the snail host. The cDNA and the gene were cloned and sequenced. The cDNA, from cap site to the poly(A) addition site, is 498 bp long. It encodes a protein of 117 amino acids with a hydrophobic signal peptide of 18 residues, indicating that SmSPO-1 is a secreted or a membranal protein. In the gene the cDNA is split into four exons spread over 2.1 kb of chromosomal DNA.
Aquaculture, 1995
Using the PDS 1000/He ballistic gene transfer apparatus from BioRad, Artemia franciscana embryos ... more Using the PDS 1000/He ballistic gene transfer apparatus from BioRad, Artemia franciscana embryos were bombarded with high velocity gold microparticles coated with a circular plasmid containing a luciferase reporter gene placed under the control of the Drosophila melanogaster hsp 70 promoter (3000 to 10 000 embryos per shot). Even for the most drastic ballistic parameters investigated on dechorionated cysts (rupture disk, 1800 psi; distance D between the stopping screen and the embryos, 35 mm), no significant luciferase activity was detected after heat shock (30 min, 41 °C). After bombarding protruding embryos obtained 20 h after dechorionated cyst rehydration, the best result in terms of embryo survival and luciferase activity was obtained for D = 35 mm with a 450-psi rupture disk. For these parameters, significant luciferase activity was observed 12 and 24 h after bombardment, but not at 48 h. In this particular model, the data suggest transient luciferase expression, with a peak of luciferase activity within the 12 h following bombardment. These results indicate that the ballistic technique is useful for studying transgene promoter efficiency in crustaceans and suggest its utility for attempting the production of transgenic animals.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2001
Tyrosine kinase receptors play a key role in the communication of cells with their environment. G... more Tyrosine kinase receptors play a key role in the communication of cells with their environment. Growth hormone receptors, such as insulin receptors, are involved in the regulation of cell growth, differentiation and metabolism in multicellular organisms. Insulin-related peptides and members of the insulin receptor subfamily have been described in a wide variety of invertebrates, including freshwater molluscs. In this paper, we describe the metabolic effect of insulin on a mollusc cell line (Bge) derived from embryos of the snail Biomphalaria glabrata. Using a PCR strategy, we have cloned from Bge cells a cDNA encoding a protein (BgIR) homologous to, and exhibiting all of the typical features of insulin receptors. Northern blot analysis confirmed the expression of BgIR in B. glabrata snails and suggested its wide distribution in the snail body. Bge cells have been shown to provide the environmental conditions necessary for the in vitro development of the sporocysts of Schistosoma mansoni, a trematode parasite that uses B. glabrata as an intermediate host. The possible implication of BgIR in the activating and proliferating processes observed in Bge cells during their coculture with S. mansoni larvae is discussed. ß
Parasitology Today, 1998
As intermediate hosts, molluscs play a major role in the transmission of schistosomes; they are t... more As intermediate hosts, molluscs play a major role in the transmission of schistosomes; they are the sites of an intense multiplication of parasites. Thus, snail control strategies are considered a priority for the reduction of schistosomiasis transmission. Here, Vinca Lardans and Colette Dissous review the efficacy of environmental management and the use of molluscicides and biological agents to control snail populations. They then describe the development of diagnostic tests, based on the detection of parasite antigens or specific parasite DNA sequences in snail tissues, to detect the early infection of snails. Finally, they discuss progress in studying the molecular basis of susceptibility and resistance phenotypes, and the possible application of the genetic manipulation of molluscs.
Parasitology Research, 1999
We have cloned from Biomphalaria glabrata, the intermediate host of the helminth parasite Schisto... more We have cloned from Biomphalaria glabrata, the intermediate host of the helminth parasite Schistosoma mansoni, a 36-kDa apparent-molecular-mass molecule (BgSel) that shares sequence identity with selectins of the cell-adhesion-molecule superfamily. BgSel exhibited in its C-terminal part a putative C-type lectin domain similar to the selectin lectin domain. Using antibodies to the recombinant BgSel protein, we demonstrated the presence of BgSel in snail hemocytes as well as in the cell line derived from B. glabrata embryos (Bge). Anti-BgSel antibodies specifically recognized a 79-kDa component in Bge-cell-secreted products that was supposed to represent the native form of BgSel, as was confirmed after glycosidase treatment. Lectins are known to be implicated in recognition mechanisms participating in humoral and cellular immunity in molluscs. The possible role of BgSel in the interaction between sporocysts and Bge cells, particularly in the in vitro model of sporocyst development dependent on Bge cell factors, remains to be determined.
Parasitology Research, 1996
... Bge cells can provide good environmental conditions for the development of mother sporocysts ... more ... Bge cells can provide good environmental conditions for the development of mother sporocysts to the daughter form (Yoshino and Laursen 1995). ... The plasmid pDr-luc contained the luci-ferase gene under the control of the heat-shock-respon-sive element from the Drosophila ...
Nucleic Acids Research, 1998
The CCAAT-binding protein NF-Y is involved in the regulation of a variety of eukaryotic genes and... more The CCAAT-binding protein NF-Y is involved in the regulation of a variety of eukaryotic genes and is formed in higher eukaryotes by three subunits NF-YA/ B/C. We have characterized NF-Y of the trematode parasite Schistosoma mansoni and studied the structure and the function of the SMNF-YA subunit. In this work, we present the cloning and sequence analysis of the B subunit of the parasite factor. SMNF-YB contains the conserved HAP-3 homology domain but the remaining part of the protein was found to be highly divergent from all other species. We demonstrated by transfections of GAL4 fusion constructs, that mouse NF-YB does not contain activation domains while the C-terminal part of SMNF-YB has transcriptional activation potential. On the other hand, the N-terminal parts of SMNF-YA and mouse NF-YA were shown to mediate transactivation; the integrity of a large 160 amino acid glutamine-rich domain of NF-YA was required for this function and an adjacent serine-and threonine-rich domain was necessary for full activity in HepG2, but redundant in other cell types. Transactivation domains identified in SMNF-YB are also rich in serine and threonine residues. Our results indicate that serine/threonine-rich sequences from helminth parasites potentiate transcription and that such structures have diverged during evolution within the same transcription factor.
Molecular and Biochemical Parasitology, 2003
Previous studies have suggested that successful development of the parasitic helminth Schistosoma... more Previous studies have suggested that successful development of the parasitic helminth Schistosoma mansoni must be dependent on an adaptative molecular dialogue with its hosts and on the existence of receptors for growth factors and hormones. Attempts to identify a homolog of the insulin receptor (IR) have led us to characterize a new receptor tyrosine kinase (RTK) molecule in S. mansoni. SmRTK-1 is an integral membrane protein with a single membrane-spanning sequence separating an extracellular ligand-binding domain and a cytoplasmic TK domain. Structural and phylogenetic analyses of the kinase domain of SmRTK-1 confirmed its similarity to IR catalytic domains. However, sequence analysis of the extracellular domain of SmRTK-1 revealed similarity with various proteins (such as drug receptors) that share a structure known as the Venus Flytrap (VFT) module. Alignment with other VFT modules for which the structure has been solved was used to generate a 3D model of the putative VFT module of SmRTK-1. Phylogenetic analysis indicated that the SmRTK-1 VFT module was closer to that of the GABA B receptor. Numerous RTK genes recently discovered in vertebrate and invertebrate species code for large families of modular proteins with diverse structures and ligand-binding specificities. SmRTK-1 probably represents a new class of RTK whose function remains to be determined. RTKs are present in all metazoans and associated with the control of metabolism, growth and development. The preferential localization of SmRTK-1 in sporocyst germinal cells and ovocytes could be in favor of its function in schistosome growth and differentiation.
Molecular and Biochemical Parasitology, 1999
Cyclosporin A (CsA) has been found to exert potent anti-parasite activity against a wide range of... more Cyclosporin A (CsA) has been found to exert potent anti-parasite activity against a wide range of protozoan and helminth parasites. In schistosomes, evidence has been accumulated to propose that the drug damages parasites by mechanisms independent of its immunosuppressive properties. Moreover, the absence of correlation between anti-schistosomal properties and inhibition of peptidyl -prolyl cis-trans isomerase activity of cyclophilins (CsA receptors) for various drug analogs, argued against a direct implication of cyclophilins in the lethal effect of CsA. We describe, in S. mansoni, the existence of NF-AT-like transcription factors, a protein family already characterized by its sensitivity to CsA. The observation that CsA treatment of S. mansoni larvae inhibited the expression of the Sm28GST protein and the characterization of a functional NF-AT-like site in the gene encoding this protein, provide new insights in the understanding of the antischistosomal effect of CsA. Our results also support the hypothesis that the regulatory function of NF-AT-like proteins might be responsible for parasite development and survival in the host and open new perspectives in studies of helminth biology.
Journal of General Virology, 1996
Mouse hepatitis viruses (MHV) diversely affect immune responses, depending on the viral strain an... more Mouse hepatitis viruses (MHV) diversely affect immune responses, depending on the viral strain and the mouse genetic background. Here, we studied the effect of MHV-A59 infection on B cell responses of 129/Sv and CBA mice. Our results indicate that in these strains, MHV-A59 induces spleen cell activation that leads to enlargement of the spleen without structural alteration. Infection triggers production by B lymphocytes of large amounts of immunoglobulin G2a, mostly without viral specificity. This polyclonal immunoglobulin production is dependent on the presence of functional T helper cells. This polyclonal B lymphocyte activation induced by MHV-A59 infection can have pathological implications, such as the enhancement of concomitant autoimmune reactions.
Experimental Parasitology, 1998
Lardans, V., Serra, E., Capron, A., and Dissous, C. 1998. Characterpromotion, transformation, and... more Lardans, V., Serra, E., Capron, A., and Dissous, C. 1998. Characterpromotion, transformation, and other signal transduction ization of an intracellular receptor for activated protein kinase C pathways. Activation of PKCs results in phosphorylation of (RACK) from the mollusc Biomphalaria glabrata, the intermediate specific proteins and their selective activity is dependent on host for Schistosoma mansoni. Experimental Parasitology 88, 194-199. specific subcellular targeting that allows their accessibility A receptor for activated protein kinase C (RACK) was characterized from the mollusc Biomphalaria glabrata, the intermediate host for to selected substrates (Liu 1996). the human parasite Schistosoma mansoni. This protein was shown to PKC isoenzymes are among the first signaling proteins possess structural and functional characteristics of other RACK proteins that have been shown to undergo translocation from the from various cells and organisms. Its ability to bind mammalian PKCs cytosol to the particulate fraction upon activation. Translocaalso confirmed the conservation of PKC and RACK interactive domains throughout evolution. Results of immunolocalization indicated the pres-tion of PKCs was first thought to reflect a direct binding of ence of Bg RACK in the cytoplasm of mollusc hemocytes and B. the enzyme to membrane lipids but further data indicated glabrata embryonic (Bge) cells with a more intense staining around that proteins could also anchor activated PKCs at the site of the nucleus. These results are in agreement with the association of translocation (Newton 1995). Many of these PKC-targeting RACK proteins with cytoskeletal elements. ᭧ 1998 Academic Press proteins, essentially implied in cytoskeleton functions, con-
Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 2001
Binding and inhibition studies reveal that the DNA-binding domain (DBD) fragment and the full-len... more Binding and inhibition studies reveal that the DNA-binding domain (DBD) fragment and the full-length molecule of the heat-shock transcription factor of schistosome (SmHSF) differ in DNA sequence recognition. SmHSF does not recognize the ideal HSE consensus sequence (nGAAnnTTCnnGAAn) but recognizes a variant HSE that contains nGTAn instead of nGAAn in the third pentamer. The DBD reacts efficiently with the ideal HSE sequence and with lower affinity with the variant HSE sequence. These findings suggest that elements inside and outside the DBD contribute to the DNA-binding specificity of HSF.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1999
Schistosomes are parasitic helminths with a complex life cycle in human and snail hosts. They exp... more Schistosomes are parasitic helminths with a complex life cycle in human and snail hosts. They express stage-specific genes that conceivably determine distinct properties of the parasite at different developmental stages. Here we report the stage-specific gene SmSPO-1, which is preferentially expressed in sporocysts residing in the snail host. The cDNA and the gene were cloned and sequenced. The cDNA, from cap site to the poly(A) addition site, is 498 bp long. It encodes a protein of 117 amino acids with a hydrophobic signal peptide of 18 residues, indicating that SmSPO-1 is a secreted or a membranal protein. In the gene the cDNA is split into four exons spread over 2.1 kb of chromosomal DNA.
Aquaculture, 1995
Using the PDS 1000/He ballistic gene transfer apparatus from BioRad, Artemia franciscana embryos ... more Using the PDS 1000/He ballistic gene transfer apparatus from BioRad, Artemia franciscana embryos were bombarded with high velocity gold microparticles coated with a circular plasmid containing a luciferase reporter gene placed under the control of the Drosophila melanogaster hsp 70 promoter (3000 to 10 000 embryos per shot). Even for the most drastic ballistic parameters investigated on dechorionated cysts (rupture disk, 1800 psi; distance D between the stopping screen and the embryos, 35 mm), no significant luciferase activity was detected after heat shock (30 min, 41 °C). After bombarding protruding embryos obtained 20 h after dechorionated cyst rehydration, the best result in terms of embryo survival and luciferase activity was obtained for D = 35 mm with a 450-psi rupture disk. For these parameters, significant luciferase activity was observed 12 and 24 h after bombardment, but not at 48 h. In this particular model, the data suggest transient luciferase expression, with a peak of luciferase activity within the 12 h following bombardment. These results indicate that the ballistic technique is useful for studying transgene promoter efficiency in crustaceans and suggest its utility for attempting the production of transgenic animals.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2001
Tyrosine kinase receptors play a key role in the communication of cells with their environment. G... more Tyrosine kinase receptors play a key role in the communication of cells with their environment. Growth hormone receptors, such as insulin receptors, are involved in the regulation of cell growth, differentiation and metabolism in multicellular organisms. Insulin-related peptides and members of the insulin receptor subfamily have been described in a wide variety of invertebrates, including freshwater molluscs. In this paper, we describe the metabolic effect of insulin on a mollusc cell line (Bge) derived from embryos of the snail Biomphalaria glabrata. Using a PCR strategy, we have cloned from Bge cells a cDNA encoding a protein (BgIR) homologous to, and exhibiting all of the typical features of insulin receptors. Northern blot analysis confirmed the expression of BgIR in B. glabrata snails and suggested its wide distribution in the snail body. Bge cells have been shown to provide the environmental conditions necessary for the in vitro development of the sporocysts of Schistosoma mansoni, a trematode parasite that uses B. glabrata as an intermediate host. The possible implication of BgIR in the activating and proliferating processes observed in Bge cells during their coculture with S. mansoni larvae is discussed. ß