Development of a model of Saint Louis encephalitis infection and disease in mice
Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis enceph...
Ausführliche Beschreibung
Autor*in: |
Marques, Rafael Elias [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2017 |
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Anmerkung: |
© The Author(s). 2017 |
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Übergeordnetes Werk: |
Enthalten in: Journal of neuroinflammation - London : BioMed Central, 2004, 14(2017), 1 vom: 22. März |
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Übergeordnetes Werk: |
volume:14 ; year:2017 ; number:1 ; day:22 ; month:03 |
Links: |
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DOI / URN: |
10.1186/s12974-017-0837-2 |
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Katalog-ID: |
SPR029107393 |
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520 | |a Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. | ||
650 | 4 | |a St. Louis encephalitis |7 (dpeaa)DE-He213 | |
650 | 4 | |a SLEV |7 (dpeaa)DE-He213 | |
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650 | 4 | |a Viral encephalitis |7 (dpeaa)DE-He213 | |
650 | 4 | |a Inflammation |7 (dpeaa)DE-He213 | |
700 | 1 | |a Del Sarto, Juliana L. |4 aut | |
700 | 1 | |a Rocha, Rebeca P. F. |4 aut | |
700 | 1 | |a Gomes, Giovanni F. |4 aut | |
700 | 1 | |a Cramer, Allysson |4 aut | |
700 | 1 | |a Rachid, Milene A. |4 aut | |
700 | 1 | |a Souza, Danielle G. |4 aut | |
700 | 1 | |a Nogueira, Maurício L. |4 aut | |
700 | 1 | |a Teixeira, Mauro M. |4 aut | |
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10.1186/s12974-017-0837-2 doi (DE-627)SPR029107393 (SPR)s12974-017-0837-2-e DE-627 ger DE-627 rakwb eng Marques, Rafael Elias verfasserin (orcid)0000-0002-6949-0947 aut Development of a model of Saint Louis encephalitis infection and disease in mice 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. St. Louis encephalitis (dpeaa)DE-He213 SLEV (dpeaa)DE-He213 Mouse model (dpeaa)DE-He213 Viral encephalitis (dpeaa)DE-He213 Inflammation (dpeaa)DE-He213 Del Sarto, Juliana L. aut Rocha, Rebeca P. F. aut Gomes, Giovanni F. aut Cramer, Allysson aut Rachid, Milene A. aut Souza, Danielle G. aut Nogueira, Maurício L. aut Teixeira, Mauro M. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 22. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:22 month:03 https://dx.doi.org/10.1186/s12974-017-0837-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 22 03 |
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10.1186/s12974-017-0837-2 doi (DE-627)SPR029107393 (SPR)s12974-017-0837-2-e DE-627 ger DE-627 rakwb eng Marques, Rafael Elias verfasserin (orcid)0000-0002-6949-0947 aut Development of a model of Saint Louis encephalitis infection and disease in mice 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. St. Louis encephalitis (dpeaa)DE-He213 SLEV (dpeaa)DE-He213 Mouse model (dpeaa)DE-He213 Viral encephalitis (dpeaa)DE-He213 Inflammation (dpeaa)DE-He213 Del Sarto, Juliana L. aut Rocha, Rebeca P. F. aut Gomes, Giovanni F. aut Cramer, Allysson aut Rachid, Milene A. aut Souza, Danielle G. aut Nogueira, Maurício L. aut Teixeira, Mauro M. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 22. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:22 month:03 https://dx.doi.org/10.1186/s12974-017-0837-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 22 03 |
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10.1186/s12974-017-0837-2 doi (DE-627)SPR029107393 (SPR)s12974-017-0837-2-e DE-627 ger DE-627 rakwb eng Marques, Rafael Elias verfasserin (orcid)0000-0002-6949-0947 aut Development of a model of Saint Louis encephalitis infection and disease in mice 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. St. Louis encephalitis (dpeaa)DE-He213 SLEV (dpeaa)DE-He213 Mouse model (dpeaa)DE-He213 Viral encephalitis (dpeaa)DE-He213 Inflammation (dpeaa)DE-He213 Del Sarto, Juliana L. aut Rocha, Rebeca P. F. aut Gomes, Giovanni F. aut Cramer, Allysson aut Rachid, Milene A. aut Souza, Danielle G. aut Nogueira, Maurício L. aut Teixeira, Mauro M. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 22. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:22 month:03 https://dx.doi.org/10.1186/s12974-017-0837-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 22 03 |
allfieldsGer |
10.1186/s12974-017-0837-2 doi (DE-627)SPR029107393 (SPR)s12974-017-0837-2-e DE-627 ger DE-627 rakwb eng Marques, Rafael Elias verfasserin (orcid)0000-0002-6949-0947 aut Development of a model of Saint Louis encephalitis infection and disease in mice 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. St. Louis encephalitis (dpeaa)DE-He213 SLEV (dpeaa)DE-He213 Mouse model (dpeaa)DE-He213 Viral encephalitis (dpeaa)DE-He213 Inflammation (dpeaa)DE-He213 Del Sarto, Juliana L. aut Rocha, Rebeca P. F. aut Gomes, Giovanni F. aut Cramer, Allysson aut Rachid, Milene A. aut Souza, Danielle G. aut Nogueira, Maurício L. aut Teixeira, Mauro M. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 22. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:22 month:03 https://dx.doi.org/10.1186/s12974-017-0837-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 22 03 |
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10.1186/s12974-017-0837-2 doi (DE-627)SPR029107393 (SPR)s12974-017-0837-2-e DE-627 ger DE-627 rakwb eng Marques, Rafael Elias verfasserin (orcid)0000-0002-6949-0947 aut Development of a model of Saint Louis encephalitis infection and disease in mice 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. St. Louis encephalitis (dpeaa)DE-He213 SLEV (dpeaa)DE-He213 Mouse model (dpeaa)DE-He213 Viral encephalitis (dpeaa)DE-He213 Inflammation (dpeaa)DE-He213 Del Sarto, Juliana L. aut Rocha, Rebeca P. F. aut Gomes, Giovanni F. aut Cramer, Allysson aut Rachid, Milene A. aut Souza, Danielle G. aut Nogueira, Maurício L. aut Teixeira, Mauro M. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 22. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:22 month:03 https://dx.doi.org/10.1186/s12974-017-0837-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 22 03 |
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Marques, Rafael Elias misc St. Louis encephalitis misc SLEV misc Mouse model misc Viral encephalitis misc Inflammation Development of a model of Saint Louis encephalitis infection and disease in mice |
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Development of a model of Saint Louis encephalitis infection and disease in mice St. Louis encephalitis (dpeaa)DE-He213 SLEV (dpeaa)DE-He213 Mouse model (dpeaa)DE-He213 Viral encephalitis (dpeaa)DE-He213 Inflammation (dpeaa)DE-He213 |
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Marques, Rafael Elias Del Sarto, Juliana L. Rocha, Rebeca P. F. Gomes, Giovanni F. Cramer, Allysson Rachid, Milene A. Souza, Danielle G. Nogueira, Maurício L. Teixeira, Mauro M. |
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development of a model of saint louis encephalitis infection and disease in mice |
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Development of a model of Saint Louis encephalitis infection and disease in mice |
abstract |
Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. © The Author(s). 2017 |
abstractGer |
Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. © The Author(s). 2017 |
abstract_unstemmed |
Background Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. Methods To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice. Results Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection. © The Author(s). 2017 |
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Del Sarto, Juliana L. Rocha, Rebeca P. F. Gomes, Giovanni F. Cramer, Allysson Rachid, Milene A. Souza, Danielle G. Nogueira, Maurício L. Teixeira, Mauro M. |
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In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively. Conclusions Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. 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