The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Ghislaine Lacroix - One of the best experts on this subject based on the ideXlab platform.
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proteomic analysis of major and minor allergens from isolated pollen Cytoplasmic Granules
Journal of Proteome Research, 2012Co-Authors: Oussama Abou Chakra, Ghislaine Lacroix, Jeanpierre Sutra, Emmanuelle Demey Thomas, Joelle Vinh, Pascal Poncet, Helene SenechalAbstract:Grass pollen is one of the most important vectors of aeroallergens. Under atmospheric conditions, pollen grains can release pollen Cytoplasmic Granules (PCGs). The allergens associated with these intrinsic subfractions induce, in laboratory animals as well as in asthmatic patients, allergic and inflammatory responses. The objectives of this study were to characterize the PCGs' intrinsic allergens and to compare them with those of pollen grains. The water-soluble proteins were extracted from pollen grains and their PCGs. IgE-binding proteins were analyzed and characterized through an allergomic strategy: 1- and 2-dimensional gel electrophoresis (1-DE and 2-DE), immunoblotting, using grass-pollen-sensitized patient sera, mass spectrometry (MS) analysis, and database searching. Several of the allergens listed in the IUIS nomenclature, Phl p 1, 4, 5, 6, and 12, were detected in pollen and PCG extracts, whereas Phl p 11 was found only in PCGs, and Phl p 2 as well as Phl p 13 were found only in pollen extract. ...
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Ability of Pollen Cytoplasmic Granules to Induce Biased Allergic Responses in a Rat Model
International Archives of Allergy and Immunology, 2011Co-Authors: Oussama Abou Chakra, Gabriel Peltre, Jeanpierre Sutra, Pascal Poncet, Helene Senechal, Françoise Rogerieux, Ghislaine LacroixAbstract:Background: Grass pollen is one of the most important aeroallergens in Europe. It highly contributes to respiratory allergic diseases, mainly allergic rhinitis. In contact to water or airborne pollutants, pollen grains can release pollen Cytoplasmic Granules (PCGs) containing allergens. Because of their size (< 5 mu m), PCGs may penetrate deeper into the lungs to induce higher allergic responses, such as asthma. They have been associated with thunderstorm-related asthma. The aim of this study was to evaluate, with Brown Norway rats, the allergenic potential of isolated PCGs and to compare it with the allergenicity of whole timothy grass pollen. Methods: Rats were sensitized (day 0) and challenged (day 21), in controlled comparative conditions, with pollen grains (0.5 mg) or PCGs (4.5 x 10(7) and 0.5 mg). At day 25, blood samples, bronchoalveolar lavage fluid (BALF) and bronchial lymph node were collected. IgE and IgG1 levels in sera were assessed by ELISA. Alveolar cells, protein and cytokine concentrations were quantified in BALF. T cell proliferation, in response to pollen or Granules, was performed by lymph node assay. Results: The results showed that proliferative responses of lymph node cells were similar in PCG- and pollen-sensitized rats. IgE and IgG1 levels were higher in pollen-than in PCG-sensitized rats. However, eosinophils, lymphocytes and pro-allergy cytokines in BALF were higher in PCG- than in pollen-sensitized rats. Conclusions: Thus, PCGs, able to deeply penetrate in the respiratory tract, induced local and strong allergic and inflammatory responses more linked with asthma-than rhinitis-related allergic symptoms.
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Key role of water-insoluble allergens of pollen Cytoplasmic Granules in biased allergic response in a rat model
World Allergy Organization Journal, 2011Co-Authors: Oussama Abou Chakra, Ghislaine Lacroix, Jeanpierre Sutra, Pascal Poncet, Helene SenechalAbstract:Background Grass pollen grain, an important aeroallergen, can disperse in the environment pollen Cytoplasmic Granules (PCGs) able to release water-soluble allergens when they are washed out by rainfall. The allergenicity of these washed PCGs is, however, preserved. Objective The purpose of the study was to assess the allergenic potential of washed and unwashed PCGs, from Phleum pratense pollen grains, in the Brown Norway rat, and to study the IgE reactivity of sera of sensitized rats to water-soluble and water-insoluble extracts of PCGs and pollen grains. Methods Rats were sensitized and challenged intratracheally with washed or unwashed PCGs or pollen grains. Using water-soluble and -insoluble extracts of pollen grains and/or PCGs, IgE ELISA and immunoblotting were performed with rat sera. Proliferation of bronchial lymph node cells was monitored by [3H]-thymidine incorporation in a lymph node assay. Alveolar cells, proteins, and TH1 and TH2 cytokines were quantified in bronchoalveolar lavage fluid. Results Rats sensitized with unwashed PCGs showed a predominant humoral response with high serum IgE and reactivity to water-soluble and -insoluble proteins together with low lymph node cell proliferation. Conversely, in rats sensitized to washed PCGs, cellular responses were higher with significant increases in eosinophils, lymphocytes, and TH2 cytokines observed in bronchoalveolar lavage fluid. Conclusion Allergic and inflammatory responses were induced by both grass pollen grains and their isolated washed and unwashed PCGs. However, on the basis of humoral and cellular responses, differential patterns were observed. Water-insoluble allergens seem to play a role in the centrally mediated inflammatory response, whereas water-soluble allergens may be involved in the peripheral humoral response.
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Immunological Interactive Effects between Pollen Grains and Their Cytoplasmic Granules on Brown Norway Rats
World Allergy Organization Journal, 2009Co-Authors: Oussama Abou Chakra, Gabriel Peltre, Helene Senechal, Françoise Rogerieux, Sutra Jean-pierre, Ghislaine LacroixAbstract:Background Grass pollen is one of the most important aeroallergen vectors in Europe. Under some meteorological factors, pollen grains can release pollen Cytoplasmic Granules (PCGs). PCGs induce allergic responses. Several studies have shown that during a period of thunderstorms the number of patients with asthma increases because of higher airborne concentrations of PCGs. Objective The aims of the study were to assess the allergenicity of interactive effects between pollen and PCGs and to compare it with allergenicity of Timothy grass pollen and PCGs in Brown Norway rats. Methods Rats were sensitized (day 0) and challenged (day 21) with pollen grains and/or PCGs. Four groups were studied: pollen-pollen (PP), PCGs-PCGs (GG), pollen-PCGs (PG), and PCGs-pollen (GP). Blood samples, bronchoalveolar lavage fluid, and bronchial lymph node were collected at day 25. IgE and IgG1 levels in sera were assessed by enzyme-linked immunosorbent assay. Alveolar cells, protein, and cytokine concentrations were quantified in bronchoalveolar lavage fluid. T-cell proliferation, in response to pollen or Granules, was performed by lymph node assay. Results Interactive effects between pollen and PCGs increased IgE and IgG1 levels when compared with those of the negative control. These increases were lower than those of the PP group but similar to the levels obtained by the GG group. Whatever was used in the sensitization and/or challenge phase, PCGs increased lymphocyte and Rantes levels compared with those of the pollen group. The interactive effects increased IL-1α and IL-1β compared with those of the PP and GG groups. Conclusions Immunologic interactive effects have been shown between pollen and PCGs. For humoral and cellular allergic responses, interactive effects between the 2 aeroallergenic sources used in this study seem to be influenced mainly by PCGs.
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traffic related air pollutants induce the release of allergen containing Cytoplasmic Granules from grass pollen
International Archives of Allergy and Immunology, 2006Co-Authors: Alexandre Motta, Gabriel Peltre, M Marliere, P A Sterenberg, Ghislaine LacroixAbstract:Background/Aim: Pollen Cytoplasmic Granules (PCG) are loaded with allergens. They are released from grass pollen grains following contact with water and can form a respirable allerg
Mark Harris - One of the best experts on this subject based on the ideXlab platform.
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persistent replication of a chikungunya virus replicon in human cells is associated with presence of stable Cytoplasmic Granules containing nonstructural protein 3
Journal of Virology, 2018Co-Authors: Roland Remenyi, Alistair Curd, Andres Merits, Carsten Zothner, Ruth E Hughes, Michelle Peckham, Mark HarrisAbstract:Chikungunya virus (CHIKV), a mosquito-borne human pathogen, causes a disabling disease characterized by severe joint pain that can persist for weeks, months, or even years in patients. The nonstructural protein 3 (nsP3) plays essential roles during acute infection, but little is known about the function of nsP3 during chronic disease. Here, we used subdiffraction multicolor microscopy for spatial and temporal analysis of CHIKV nsP3 within human cells that persistently replicate replicon RNA. Round Cytoplasmic Granules of various sizes (i) contained nsP3 and stress granule assembly factors 1 and 2 (G3BP1/2), (ii) were next to double-stranded RNA foci and nsP1-positive structures, and (iii) were close to the nuclear membrane and the nuclear pore complex protein Nup98. Analysis of protein turnover and mobility by live-cell microscopy revealed that the Granules could persist for hours to days, accumulated newly synthesized protein, and moved through the cytoplasm at various speeds. The Granules also had a static internal architecture and were stable in cell lysates. Refractory cells that had cleared the noncytotoxic replicon regained the ability to respond to arsenite-induced stress. In summary, nsP3 can form uniquely stable granular structures that persist long-term within the host cell. This continued presence of viral and cellular protein complexes has implications for the study of the pathogenic consequences of lingering CHIKV infection and the development of strategies to mitigate the burden of chronic musculoskeletal disease brought about by a medically important arthropod-borne virus (arbovirus). IMPORTANCE Chikungunya virus (CHIKV) is a reemerging alphavirus transmitted by mosquitos and causes transient sickness but also chronic disease affecting muscles and joints. No approved vaccines or antivirals are available. Thus, a better understanding of the viral life cycle and the role of viral proteins can aid in identifying new therapeutic targets. Advances in microscopy and development of noncytotoxic replicons (A. Utt, P. K. Das, M. Varjak, V. Lulla, A. Lulla, A. Merits, J Virol 89:3145–3162, 2015, https://doi.org/10.1128/JVI.03213-14) have allowed researchers to study viral proteins within controlled laboratory environments over extended durations. Here we established human cells that stably replicate replicon RNA and express tagged nonstructural protein 3 (nsP3). The ability to track nsP3 within the host cell and during persistent replication can benefit fundamental research efforts to better understand long-term consequences of the persistence of viral protein complexes and thereby provide the foundation for new therapeutic targets to control CHIKV infection and treat chronic disease symptoms.
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persistent chikungunya virus replication in human cells is associated with presence of stable Cytoplasmic Granules containing non structural protein 3
bioRxiv, 2018Co-Authors: Roland Remenyi, Alistair Curd, Andres Merits, Carsten Zothner, Ruth E Hughes, Michelle Peckham, Yanni Gao, Mark HarrisAbstract:Chikungunya virus (CHIKV), a mosquito-borne human pathogen, causes a disabling disease characterized by severe joint pain that can persist for weeks, months or even years in patients. The non-structural protein 3 (nsP3) plays essential roles during acute infection, but little is known about the function of nsP3 during chronic disease. Here, we used sub-diffraction multi-color microscopy for a spatial and temporal analysis of CHIKV nsP3 within human cells that persistently replicate viral RNA. Round Cytoplasmic Granules of various sizes (i) contained nsP3 and G3BP Stress Granule Assembly factor; (ii) were next to double-stranded RNA foci, and nsP1-positive structures; and (iii) made contact with markers of the cytoskeleton and cellular structures, such as early endosomes and nucleopores. Analysis of protein turnover and mobility by live-cell microscopy revealed that Granules could persist for hours to days, can accumulate newly synthesized protein, and move differently through the cytoplasm. Granules also had a static internal architecture and were stable in cell lysates. Whereas cells with active replication and stable nsP3-Granules did not respond to oxidative stress, refractory cells that had cleared the non-cytotoxic replicon could. In summary, nsP3 can form uniquely stable granular structures that persist long-term within the host cell. This continued presence of viral and cellular protein-complexes has implications for the study of the pathogenic consequences of lingering CHIKV infection and the development of strategies to mitigate the burden of chronic musculoskeletal disease brought about by a medically important arthropod-borne virus (arbovirus).
Carlos Cordoncardo - One of the best experts on this subject based on the ideXlab platform.
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the precrystalline Cytoplasmic Granules of alveolar soft part sarcoma contain monocarboxylate transporter 1 and cd147
American Journal of Pathology, 2002Co-Authors: Marc Ladanyi, Marija Drobnjak, Ann Baren, David W. Golde, Cristina R Antonescu, Carlos CordoncardoAbstract:Alveolar soft part sarcoma (ASPS) is an unusual tumor of young adults with the characteristic presence on ultrastructural analysis of rhomboid or rectangular Cytoplasmic crystals. These membrane-bound crystals are known to form within specific PAS-diastase-resistant electron-dense Cytoplasmic Granules. The composition of these crystals and the dense Granules from which they are derived has remained elusive. After the detection of strong discrete granular Cytoplasmic immunoreactivity in ASPS for monocarboxylate transporter 1 (MCT1) in the course of a broad immunohistochemical characterization of an MCT1 antibody, we studied the expression of MCT1 and its interacting partner, CD147, in a panel of 10 ASPS cases using appropriate antibodies. MCT1 is one of a family of widely expressed proton-linked transporters for monocarboxylates such as lactate and pyruvate. In all normal and neoplastic tissues studied to date, MCT1 immunoreactivity is limited to the cell surface. We find that the periodic acid-Schiff-diastase-resistant Cytoplasmic Granules of ASPS are strongly immunoreactive for MCT1 and CD147. Specifically, intense Cytoplasmic granular positivity for MCT1 and CD147 was found in 7 of 10 and 8 of 10 ASPSs, respectively. Ultrastructural immunohistochemistry with immunogold labeling confirmed that the MCT1 immunoreactivity localized to the Cytoplasmic electron-dense Granules in ASPS. Western blot analysis of several ASPS cases confirmed that the protein reactive with the MCT1 antibody and that reactive with the CD147 antibody both migrated at the size expected for MCT1 and CD147, respectively. Thus, ASPS cells seem to accumulate MCT1-CD147 complexes in the specific Cytoplasmic Granules known to undergo crystallization. The possible basis for the overproduction or impaired surface localization of these proteins in ASPS remains unclear.
Helene Senechal - One of the best experts on this subject based on the ideXlab platform.
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proteomic analysis of major and minor allergens from isolated pollen Cytoplasmic Granules
Journal of Proteome Research, 2012Co-Authors: Oussama Abou Chakra, Ghislaine Lacroix, Jeanpierre Sutra, Emmanuelle Demey Thomas, Joelle Vinh, Pascal Poncet, Helene SenechalAbstract:Grass pollen is one of the most important vectors of aeroallergens. Under atmospheric conditions, pollen grains can release pollen Cytoplasmic Granules (PCGs). The allergens associated with these intrinsic subfractions induce, in laboratory animals as well as in asthmatic patients, allergic and inflammatory responses. The objectives of this study were to characterize the PCGs' intrinsic allergens and to compare them with those of pollen grains. The water-soluble proteins were extracted from pollen grains and their PCGs. IgE-binding proteins were analyzed and characterized through an allergomic strategy: 1- and 2-dimensional gel electrophoresis (1-DE and 2-DE), immunoblotting, using grass-pollen-sensitized patient sera, mass spectrometry (MS) analysis, and database searching. Several of the allergens listed in the IUIS nomenclature, Phl p 1, 4, 5, 6, and 12, were detected in pollen and PCG extracts, whereas Phl p 11 was found only in PCGs, and Phl p 2 as well as Phl p 13 were found only in pollen extract. ...
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Ability of Pollen Cytoplasmic Granules to Induce Biased Allergic Responses in a Rat Model
International Archives of Allergy and Immunology, 2011Co-Authors: Oussama Abou Chakra, Gabriel Peltre, Jeanpierre Sutra, Pascal Poncet, Helene Senechal, Françoise Rogerieux, Ghislaine LacroixAbstract:Background: Grass pollen is one of the most important aeroallergens in Europe. It highly contributes to respiratory allergic diseases, mainly allergic rhinitis. In contact to water or airborne pollutants, pollen grains can release pollen Cytoplasmic Granules (PCGs) containing allergens. Because of their size (< 5 mu m), PCGs may penetrate deeper into the lungs to induce higher allergic responses, such as asthma. They have been associated with thunderstorm-related asthma. The aim of this study was to evaluate, with Brown Norway rats, the allergenic potential of isolated PCGs and to compare it with the allergenicity of whole timothy grass pollen. Methods: Rats were sensitized (day 0) and challenged (day 21), in controlled comparative conditions, with pollen grains (0.5 mg) or PCGs (4.5 x 10(7) and 0.5 mg). At day 25, blood samples, bronchoalveolar lavage fluid (BALF) and bronchial lymph node were collected. IgE and IgG1 levels in sera were assessed by ELISA. Alveolar cells, protein and cytokine concentrations were quantified in BALF. T cell proliferation, in response to pollen or Granules, was performed by lymph node assay. Results: The results showed that proliferative responses of lymph node cells were similar in PCG- and pollen-sensitized rats. IgE and IgG1 levels were higher in pollen-than in PCG-sensitized rats. However, eosinophils, lymphocytes and pro-allergy cytokines in BALF were higher in PCG- than in pollen-sensitized rats. Conclusions: Thus, PCGs, able to deeply penetrate in the respiratory tract, induced local and strong allergic and inflammatory responses more linked with asthma-than rhinitis-related allergic symptoms.
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Key role of water-insoluble allergens of pollen Cytoplasmic Granules in biased allergic response in a rat model
World Allergy Organization Journal, 2011Co-Authors: Oussama Abou Chakra, Ghislaine Lacroix, Jeanpierre Sutra, Pascal Poncet, Helene SenechalAbstract:Background Grass pollen grain, an important aeroallergen, can disperse in the environment pollen Cytoplasmic Granules (PCGs) able to release water-soluble allergens when they are washed out by rainfall. The allergenicity of these washed PCGs is, however, preserved. Objective The purpose of the study was to assess the allergenic potential of washed and unwashed PCGs, from Phleum pratense pollen grains, in the Brown Norway rat, and to study the IgE reactivity of sera of sensitized rats to water-soluble and water-insoluble extracts of PCGs and pollen grains. Methods Rats were sensitized and challenged intratracheally with washed or unwashed PCGs or pollen grains. Using water-soluble and -insoluble extracts of pollen grains and/or PCGs, IgE ELISA and immunoblotting were performed with rat sera. Proliferation of bronchial lymph node cells was monitored by [3H]-thymidine incorporation in a lymph node assay. Alveolar cells, proteins, and TH1 and TH2 cytokines were quantified in bronchoalveolar lavage fluid. Results Rats sensitized with unwashed PCGs showed a predominant humoral response with high serum IgE and reactivity to water-soluble and -insoluble proteins together with low lymph node cell proliferation. Conversely, in rats sensitized to washed PCGs, cellular responses were higher with significant increases in eosinophils, lymphocytes, and TH2 cytokines observed in bronchoalveolar lavage fluid. Conclusion Allergic and inflammatory responses were induced by both grass pollen grains and their isolated washed and unwashed PCGs. However, on the basis of humoral and cellular responses, differential patterns were observed. Water-insoluble allergens seem to play a role in the centrally mediated inflammatory response, whereas water-soluble allergens may be involved in the peripheral humoral response.
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Immunological Interactive Effects between Pollen Grains and Their Cytoplasmic Granules on Brown Norway Rats
World Allergy Organization Journal, 2009Co-Authors: Oussama Abou Chakra, Gabriel Peltre, Helene Senechal, Françoise Rogerieux, Sutra Jean-pierre, Ghislaine LacroixAbstract:Background Grass pollen is one of the most important aeroallergen vectors in Europe. Under some meteorological factors, pollen grains can release pollen Cytoplasmic Granules (PCGs). PCGs induce allergic responses. Several studies have shown that during a period of thunderstorms the number of patients with asthma increases because of higher airborne concentrations of PCGs. Objective The aims of the study were to assess the allergenicity of interactive effects between pollen and PCGs and to compare it with allergenicity of Timothy grass pollen and PCGs in Brown Norway rats. Methods Rats were sensitized (day 0) and challenged (day 21) with pollen grains and/or PCGs. Four groups were studied: pollen-pollen (PP), PCGs-PCGs (GG), pollen-PCGs (PG), and PCGs-pollen (GP). Blood samples, bronchoalveolar lavage fluid, and bronchial lymph node were collected at day 25. IgE and IgG1 levels in sera were assessed by enzyme-linked immunosorbent assay. Alveolar cells, protein, and cytokine concentrations were quantified in bronchoalveolar lavage fluid. T-cell proliferation, in response to pollen or Granules, was performed by lymph node assay. Results Interactive effects between pollen and PCGs increased IgE and IgG1 levels when compared with those of the negative control. These increases were lower than those of the PP group but similar to the levels obtained by the GG group. Whatever was used in the sensitization and/or challenge phase, PCGs increased lymphocyte and Rantes levels compared with those of the pollen group. The interactive effects increased IL-1α and IL-1β compared with those of the PP and GG groups. Conclusions Immunologic interactive effects have been shown between pollen and PCGs. For humoral and cellular allergic responses, interactive effects between the 2 aeroallergenic sources used in this study seem to be influenced mainly by PCGs.
Roland Remenyi - One of the best experts on this subject based on the ideXlab platform.
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persistent replication of a chikungunya virus replicon in human cells is associated with presence of stable Cytoplasmic Granules containing nonstructural protein 3
Journal of Virology, 2018Co-Authors: Roland Remenyi, Alistair Curd, Andres Merits, Carsten Zothner, Ruth E Hughes, Michelle Peckham, Mark HarrisAbstract:Chikungunya virus (CHIKV), a mosquito-borne human pathogen, causes a disabling disease characterized by severe joint pain that can persist for weeks, months, or even years in patients. The nonstructural protein 3 (nsP3) plays essential roles during acute infection, but little is known about the function of nsP3 during chronic disease. Here, we used subdiffraction multicolor microscopy for spatial and temporal analysis of CHIKV nsP3 within human cells that persistently replicate replicon RNA. Round Cytoplasmic Granules of various sizes (i) contained nsP3 and stress granule assembly factors 1 and 2 (G3BP1/2), (ii) were next to double-stranded RNA foci and nsP1-positive structures, and (iii) were close to the nuclear membrane and the nuclear pore complex protein Nup98. Analysis of protein turnover and mobility by live-cell microscopy revealed that the Granules could persist for hours to days, accumulated newly synthesized protein, and moved through the cytoplasm at various speeds. The Granules also had a static internal architecture and were stable in cell lysates. Refractory cells that had cleared the noncytotoxic replicon regained the ability to respond to arsenite-induced stress. In summary, nsP3 can form uniquely stable granular structures that persist long-term within the host cell. This continued presence of viral and cellular protein complexes has implications for the study of the pathogenic consequences of lingering CHIKV infection and the development of strategies to mitigate the burden of chronic musculoskeletal disease brought about by a medically important arthropod-borne virus (arbovirus). IMPORTANCE Chikungunya virus (CHIKV) is a reemerging alphavirus transmitted by mosquitos and causes transient sickness but also chronic disease affecting muscles and joints. No approved vaccines or antivirals are available. Thus, a better understanding of the viral life cycle and the role of viral proteins can aid in identifying new therapeutic targets. Advances in microscopy and development of noncytotoxic replicons (A. Utt, P. K. Das, M. Varjak, V. Lulla, A. Lulla, A. Merits, J Virol 89:3145–3162, 2015, https://doi.org/10.1128/JVI.03213-14) have allowed researchers to study viral proteins within controlled laboratory environments over extended durations. Here we established human cells that stably replicate replicon RNA and express tagged nonstructural protein 3 (nsP3). The ability to track nsP3 within the host cell and during persistent replication can benefit fundamental research efforts to better understand long-term consequences of the persistence of viral protein complexes and thereby provide the foundation for new therapeutic targets to control CHIKV infection and treat chronic disease symptoms.
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persistent chikungunya virus replication in human cells is associated with presence of stable Cytoplasmic Granules containing non structural protein 3
bioRxiv, 2018Co-Authors: Roland Remenyi, Alistair Curd, Andres Merits, Carsten Zothner, Ruth E Hughes, Michelle Peckham, Yanni Gao, Mark HarrisAbstract:Chikungunya virus (CHIKV), a mosquito-borne human pathogen, causes a disabling disease characterized by severe joint pain that can persist for weeks, months or even years in patients. The non-structural protein 3 (nsP3) plays essential roles during acute infection, but little is known about the function of nsP3 during chronic disease. Here, we used sub-diffraction multi-color microscopy for a spatial and temporal analysis of CHIKV nsP3 within human cells that persistently replicate viral RNA. Round Cytoplasmic Granules of various sizes (i) contained nsP3 and G3BP Stress Granule Assembly factor; (ii) were next to double-stranded RNA foci, and nsP1-positive structures; and (iii) made contact with markers of the cytoskeleton and cellular structures, such as early endosomes and nucleopores. Analysis of protein turnover and mobility by live-cell microscopy revealed that Granules could persist for hours to days, can accumulate newly synthesized protein, and move differently through the cytoplasm. Granules also had a static internal architecture and were stable in cell lysates. Whereas cells with active replication and stable nsP3-Granules did not respond to oxidative stress, refractory cells that had cleared the non-cytotoxic replicon could. In summary, nsP3 can form uniquely stable granular structures that persist long-term within the host cell. This continued presence of viral and cellular protein-complexes has implications for the study of the pathogenic consequences of lingering CHIKV infection and the development of strategies to mitigate the burden of chronic musculoskeletal disease brought about by a medically important arthropod-borne virus (arbovirus).
