Author:
- Introduction
- Materials and Methods
- Animals.
- Virus.
- Infection of mice by ROCV and negative controls.
- Animal sacrifice and nervous tissue collection.
- Tissue preparations.
- RNA extraction, reverse transcription, PCR, and nested PCR for ROCV detection.
- Quantitative analysis of cytokine mRNA by real-time PCR.
- Detection of degenerated neurons by fluoro-jade B staining.
- Statistical analysis.
- Results
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Gould EA, De Lamballerie X, Zanotto PA, Holmes EC, 2003. Origins, evolution, and vector/host coadaptations within the genus Flavivirus. Adv Virus Res 59: 277–314.
-
2.
Rice CM, Lenches EM, Eddy SR, Shin SJ, Sheets RL, Straus SJH, 1985. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 229: 726–733.
-
3.
Chambers TJ, Mccourt DW, Rice CM, 1990. Production of yellow fever virus proteins in infected cells: identification of discrete polyprotein species and analysis of cleavage kinetics using region-specific polyclonal antisera. Virology 177: 159–174.
-
4.
Kuno G, Chang GJ, Tsuchiya KR, Karabatsos N, Cropp CB, 1998. Phylogeny of the genus Flavivirus. J Virol 72: 73–83.
-
5.
Medeiros DB, Nunes MR, Vasconcelos FC, Chang GJ, Kuno K, 2007. Complete genome characterization of Rocio virus (Flavivirus: Flaviviridae), a Brazilian flavivirus isolated from a fatal case of encephalitis during an epidemic in São Paulo state. J Gen Virol 88: 2237–2246.
-
6.
Lopes OS, Sacchetta AL, Francy DB, Jakob WL, Calisher CH, 1981. Emergence of a new arbovirus disease in Brazil. III. Isolation of Rocio virus from Psorophora ferox. Am J Epidemiol 113: 122–125.
-
7.
Vasconcelos PF, Rosa AP, Dégallier N, Rosa JF, Pinheiro FP, 1992. Clinical and eco-epidemiological situation of human arboviruses in Brazilian Amazonia. J Brazilian Assoc Adv Science 44: 117–124.
-
8.
Vasconcelos PF, Rosa AP, Pinheiro FP, Shope RE, Rosa JF, Rodrigues SG, Dégallier N, Travassos Da Rosa ES, 1998. Arboviruses pathogenic for man in Brazil. Rosa AP, Vasconcelos PF, Rosa JF, eds. An Overview of Arbovirology in Brazil and Neighboring Countries. Belém: Instituto Evandro Chagas, 72–99.
-
9.
Mitchell CJ, Monath TP, Cropp CB, 1981. Experimental transmission of rocio virus by mosquitoes. Am J Trop Med Hyg 30: 465–472.
-
10.
Lopes OS, 1978. Rocio (Roc) strain: SP H 34675. Am J Trop Med Hyg 27: 418–419.
-
11.
Lopes OS, Coimbra TL, Sachetta LA, Calisher CH, 1978. Emergence of a new arbovirus disease in Brazil. I. Isolation and characterization of the etiologic agent, Rocio virus. Am J Epidemiol 107: 444–449.
-
12.
Tiriba AC, 1975. Epidemia de Encefalite Atribuída a Arbovírus. Ocorrida no Litoral Sul do Estado de São Paulo em 1975: Contribuição Para o Estudo Clínico. São Paulo, Tese livre-Docência: Escola Paulista de Mecidina.
-
13.
Iversson LB, Tiriba AC, 1997. Encefalite por arbovírus Rocio. Veronesi R, Focaccia R, eds., Tratado de Infectologia Atheneu, São Paulo, 233–239.
-
14.
Travassos Da Rosa JF, Travassos Da Rosa AP, Vasconcelos PF, Rodrigues SG, Travassos Da Rosa ES, Dias LB, Cruzi AC, 1998. Arboviruses isolated in the Evandro Chagas Institute, including some described for the first time in the Brazilian Amazon region, their known hosts, and their pathology form man. Travassos AP, Vasconcelos PF, Travassos Da Rosa JE, eds. An Overview of Arbovirology on Brazil and Neighboring Countries. Belém: Instituto Evandro Chagas, 19–31.
-
15.
Chávez JH, Figueiredo LT, 2006. Emergent flaviviruses of the Japanese encephalitis complex in Brazil. Virus Rev Res 11: 28–32.
-
16.
Bronzoni RV, Baleotti FG, Nogueira RM, Nunes M, Figueiredo LT, 2005. Duplex reverse transcription-PCR followed by nested PCR assays for detection and identification of Brazilian alphaviruses and flaviviruses. J Clin Microbiol 43: 696–702.
-
17.
Schumed LC, Hopkins KJ, 2000. Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874: 123–130.
-
18.
Garlet GP, Cardoso CR, Campanelli AP, Ferreira BR, Avila-Campos MJ, Cunha FQ, Silva JS, 2006. The dual role of p55 tumor necrosis factor-α receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction. Clin Exp Immunol 147: 128–138.
-
19.
Figueiredo LT, 2000. The Brazilian flaviviruses. Microbes Infect 2: 1643–1649.
-
20.
Beasley DW, Li L, Suderman MT, Barrett AD, 2002. Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype. Virology 296: 17–23.
-
21.
Fujii Y, Kazutaka K, Kazuo N, Takasaki T, Suzuki R, Kurane I, 2008. Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice. J Infect Dis 61: 40–48.
-
22.
Haseloff RF, Blasig IE, Bauer HC, Bauer H, 2005. In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro. Cell Mol Neurobiol 25: 25–39.
-
23.
Samuel MA, Wang H, Venkatraman S, Morrey JD, Diamond MS, 2007. Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis. Proc Natl Acad Sci USA 23: 17140–17145.
-
24.
Ghoshal A, Sulagna D, Ghosh S, Mishra MK, Sharma V, Koli P, Sen E, Basu A, 2007. Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 55: 483–496.
-
25.
Xiao SY, Guzman H, Zhang H, Travassos Da Rosa AP, Tesh RB, 2001. West Nile virus infection in the golden hamster Mesocricetus auratus: a model for West Nile encephalitis. Emerg Infect Dis 7: 714–721.
-
26.
Matthews V, Robertson T, Kendrick T, Abdo M, Papadimitriou J, Mcminn P, 2000. Morphological features of Murray Valley encephalitis virus infection in the central nervous system of Swiss mice. Int J Exp Pathol 81: 31–40.
-
27.
Abbas AK, Lichtman AH, 2005. Citocinas. Abbas AK, Lichtman AH, eds. Imunologia Celular e Molecular 5° Edição. Rio de Janeiro, Brazil: Elsevier Editora Ltda., 268–269.
-
28.
Barca OS, Ferre M, Seoane JM, Prieto M, Lema R, Senaris V, Arce M, 2003. Interferon beta promotes survival in primary astrocytes through phosphatidylinositol 3-kinase. J Neuroimmunol 139: 155–159.
-
29.
De G, 2003. Immune responses to RNA-virus infections of the CNS. Nat Rev Immunol 3: 493–502.
-
30.
Shrestha B, Wang T, Samuel MA, Whitby K, Craft J, Fikrig E, Diamond MS, 2006. Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection. J Virol 80: 5338–5348.
-
31.
Liu T, Chambers TJ, 2001. Yellow fever virus encephalitis: properties of the brain associated T-cell response during virus clearance in normal and gamma interferon-deficient mice and requirement for CD4 lymphocytes. J Virol 75: 2107–2118.
-
32.
Swarup V, Ghosh J, Duseja R, Ghosh S, Basu A, 2007. Japanese encephalitis virus infection decrease endogenous IL-10 production: correlation with microglial activation and neuronal death. Neurosci Lett 420: 144–149.
-
33.
Diniz JA, Da Rosa AP, Guzman H, Xu F, Xiao SY, Popov VL, Vasconcelos PF, Tesh RB, 2006. West Nile virus infection of primary mouse neuronal and neuroglial cells: the role of astrocytes in chronic infection. Am J Trop Med Hyg 75: 691–696.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 20 | 20 | 3 |
| Full Text Views | 293 | 71 | 0 |
| PDF Downloads | 57 | 14 | 0 |
An Experimental Model of Meningoencephalomyelitis by Rocio Flavivirus in Balb/C Mice: Inflammatory Response, Cytokine Production, and Histopathology
Veridiana Ester Dias de Barros
Veridiana Ester Dias de Barros
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Fabiano P. Saggioro
Fabiano P. Saggioro
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Luciano Neder
Luciano Neder
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Rafael Freitas de Oliveira França
Rafael Freitas de Oliveira França
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Viviane Mariguela
Viviane Mariguela
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Juliana Helena Chávez
Juliana Helena Chávez
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Sandra Penharvel
Sandra Penharvel
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Jorge Forjaz
Jorge Forjaz
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Benedito Antônio Lopes da Fonseca
Benedito Antônio Lopes da Fonseca
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Luiz Tadeu Moraes Figueiredo
Luiz Tadeu Moraes Figueiredo
Virology Research Center, Department of Pathology, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil
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Rocio virus (ROCV) is a flavivirus, probably transmitted by Culex mosquitoes and maintained in nature as a zoonosis of wild birds. Rocio virus caused a human epidemic of severe encephalitis that lasted from 1973 to 1980 in the Ribeira valley, in the southeastern coast of Brazil. After this outbreak, serologic evidence of ROCV circulation has been reported and public health authorities are concerned about a return of ROCV outbreaks in Brazil. We show here a study on the pathogenesis and the physiopathology of ROCV disease in the central nervous system of a Balb/C young adult mice experimental model. The animals were intraperitoneally infected by ROCV and followed from 0 to 9 days after infection, when all of them died. Nervous tissue samples were collected from infected animals for immunohistochemistry and molecular biology analysis. We observed the virus in the central nervous system, the inflammatory changes induced by Th1 and Th2 cytokines, and the final irreversible damage of nervous tissues by neuronal degeneration and apoptosis. These findings can help to better understand the pathogenesis and physiopathology of the human meningoencephalomyelitis by ROCV and other flaviviruses.
Author Notes
Financial support: We are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) (141893/2005-2) for supporting this study.
Authors' addresses: Veridiana Ester Dias de Barros, Rafael Freitas de Oliveira França, Viviane Mariguela, Juliana Helena Chávez, Benedito Antônio Lopes da Fonseca, and Luiz Tadeu Moraes Figueiredo, Virology Research Center, University of São Paulo, São Paulo, Brazil. Fabiano Saggioro and Luciano Neder, Department of Pathology, University of São Paulo, São Paulo, Brazil. Sandra Penharvel and Jorge Forjaz, Department of Surgery and Anatomy of the School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
- Introduction
- Materials and Methods
- Animals.
- Virus.
- Infection of mice by ROCV and negative controls.
- Animal sacrifice and nervous tissue collection.
- Tissue preparations.
- RNA extraction, reverse transcription, PCR, and nested PCR for ROCV detection.
- Quantitative analysis of cytokine mRNA by real-time PCR.
- Detection of degenerated neurons by fluoro-jade B staining.
- Statistical analysis.
- Results
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Gould EA, De Lamballerie X, Zanotto PA, Holmes EC, 2003. Origins, evolution, and vector/host coadaptations within the genus Flavivirus. Adv Virus Res 59: 277–314.
-
2.
Rice CM, Lenches EM, Eddy SR, Shin SJ, Sheets RL, Straus SJH, 1985. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 229: 726–733.
-
3.
Chambers TJ, Mccourt DW, Rice CM, 1990. Production of yellow fever virus proteins in infected cells: identification of discrete polyprotein species and analysis of cleavage kinetics using region-specific polyclonal antisera. Virology 177: 159–174.
-
4.
Kuno G, Chang GJ, Tsuchiya KR, Karabatsos N, Cropp CB, 1998. Phylogeny of the genus Flavivirus. J Virol 72: 73–83.
-
5.
Medeiros DB, Nunes MR, Vasconcelos FC, Chang GJ, Kuno K, 2007. Complete genome characterization of Rocio virus (Flavivirus: Flaviviridae), a Brazilian flavivirus isolated from a fatal case of encephalitis during an epidemic in São Paulo state. J Gen Virol 88: 2237–2246.
-
6.
Lopes OS, Sacchetta AL, Francy DB, Jakob WL, Calisher CH, 1981. Emergence of a new arbovirus disease in Brazil. III. Isolation of Rocio virus from Psorophora ferox. Am J Epidemiol 113: 122–125.
-
7.
Vasconcelos PF, Rosa AP, Dégallier N, Rosa JF, Pinheiro FP, 1992. Clinical and eco-epidemiological situation of human arboviruses in Brazilian Amazonia. J Brazilian Assoc Adv Science 44: 117–124.
-
8.
Vasconcelos PF, Rosa AP, Pinheiro FP, Shope RE, Rosa JF, Rodrigues SG, Dégallier N, Travassos Da Rosa ES, 1998. Arboviruses pathogenic for man in Brazil. Rosa AP, Vasconcelos PF, Rosa JF, eds. An Overview of Arbovirology in Brazil and Neighboring Countries. Belém: Instituto Evandro Chagas, 72–99.
-
9.
Mitchell CJ, Monath TP, Cropp CB, 1981. Experimental transmission of rocio virus by mosquitoes. Am J Trop Med Hyg 30: 465–472.
-
10.
Lopes OS, 1978. Rocio (Roc) strain: SP H 34675. Am J Trop Med Hyg 27: 418–419.
-
11.
Lopes OS, Coimbra TL, Sachetta LA, Calisher CH, 1978. Emergence of a new arbovirus disease in Brazil. I. Isolation and characterization of the etiologic agent, Rocio virus. Am J Epidemiol 107: 444–449.
-
12.
Tiriba AC, 1975. Epidemia de Encefalite Atribuída a Arbovírus. Ocorrida no Litoral Sul do Estado de São Paulo em 1975: Contribuição Para o Estudo Clínico. São Paulo, Tese livre-Docência: Escola Paulista de Mecidina.
-
13.
Iversson LB, Tiriba AC, 1997. Encefalite por arbovírus Rocio. Veronesi R, Focaccia R, eds., Tratado de Infectologia Atheneu, São Paulo, 233–239.
-
14.
Travassos Da Rosa JF, Travassos Da Rosa AP, Vasconcelos PF, Rodrigues SG, Travassos Da Rosa ES, Dias LB, Cruzi AC, 1998. Arboviruses isolated in the Evandro Chagas Institute, including some described for the first time in the Brazilian Amazon region, their known hosts, and their pathology form man. Travassos AP, Vasconcelos PF, Travassos Da Rosa JE, eds. An Overview of Arbovirology on Brazil and Neighboring Countries. Belém: Instituto Evandro Chagas, 19–31.
-
15.
Chávez JH, Figueiredo LT, 2006. Emergent flaviviruses of the Japanese encephalitis complex in Brazil. Virus Rev Res 11: 28–32.
-
16.
Bronzoni RV, Baleotti FG, Nogueira RM, Nunes M, Figueiredo LT, 2005. Duplex reverse transcription-PCR followed by nested PCR assays for detection and identification of Brazilian alphaviruses and flaviviruses. J Clin Microbiol 43: 696–702.
-
17.
Schumed LC, Hopkins KJ, 2000. Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874: 123–130.
-
18.
Garlet GP, Cardoso CR, Campanelli AP, Ferreira BR, Avila-Campos MJ, Cunha FQ, Silva JS, 2006. The dual role of p55 tumor necrosis factor-α receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction. Clin Exp Immunol 147: 128–138.
-
19.
Figueiredo LT, 2000. The Brazilian flaviviruses. Microbes Infect 2: 1643–1649.
-
20.
Beasley DW, Li L, Suderman MT, Barrett AD, 2002. Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype. Virology 296: 17–23.
-
21.
Fujii Y, Kazutaka K, Kazuo N, Takasaki T, Suzuki R, Kurane I, 2008. Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice. J Infect Dis 61: 40–48.
-
22.
Haseloff RF, Blasig IE, Bauer HC, Bauer H, 2005. In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro. Cell Mol Neurobiol 25: 25–39.
-
23.
Samuel MA, Wang H, Venkatraman S, Morrey JD, Diamond MS, 2007. Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis. Proc Natl Acad Sci USA 23: 17140–17145.
-
24.
Ghoshal A, Sulagna D, Ghosh S, Mishra MK, Sharma V, Koli P, Sen E, Basu A, 2007. Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 55: 483–496.
-
25.
Xiao SY, Guzman H, Zhang H, Travassos Da Rosa AP, Tesh RB, 2001. West Nile virus infection in the golden hamster Mesocricetus auratus: a model for West Nile encephalitis. Emerg Infect Dis 7: 714–721.
-
26.
Matthews V, Robertson T, Kendrick T, Abdo M, Papadimitriou J, Mcminn P, 2000. Morphological features of Murray Valley encephalitis virus infection in the central nervous system of Swiss mice. Int J Exp Pathol 81: 31–40.
-
27.
Abbas AK, Lichtman AH, 2005. Citocinas. Abbas AK, Lichtman AH, eds. Imunologia Celular e Molecular 5° Edição. Rio de Janeiro, Brazil: Elsevier Editora Ltda., 268–269.
-
28.
Barca OS, Ferre M, Seoane JM, Prieto M, Lema R, Senaris V, Arce M, 2003. Interferon beta promotes survival in primary astrocytes through phosphatidylinositol 3-kinase. J Neuroimmunol 139: 155–159.
-
29.
De G, 2003. Immune responses to RNA-virus infections of the CNS. Nat Rev Immunol 3: 493–502.
-
30.
Shrestha B, Wang T, Samuel MA, Whitby K, Craft J, Fikrig E, Diamond MS, 2006. Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection. J Virol 80: 5338–5348.
-
31.
Liu T, Chambers TJ, 2001. Yellow fever virus encephalitis: properties of the brain associated T-cell response during virus clearance in normal and gamma interferon-deficient mice and requirement for CD4 lymphocytes. J Virol 75: 2107–2118.
-
32.
Swarup V, Ghosh J, Duseja R, Ghosh S, Basu A, 2007. Japanese encephalitis virus infection decrease endogenous IL-10 production: correlation with microglial activation and neuronal death. Neurosci Lett 420: 144–149.
-
33.
Diniz JA, Da Rosa AP, Guzman H, Xu F, Xiao SY, Popov VL, Vasconcelos PF, Tesh RB, 2006. West Nile virus infection of primary mouse neuronal and neuroglial cells: the role of astrocytes in chronic infection. Am J Trop Med Hyg 75: 691–696.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 20 | 20 | 3 |
| Full Text Views | 293 | 71 | 0 |
| PDF Downloads | 57 | 14 | 0 |