WEST NILE VIRUS INFECTION OF PRIMARY MOUSE NEURONAL AND NEUROGLIAL CELLS: THE ROLE OF ASTROCYTES IN CHRONIC INFECTION

JOSE A. P. DINIZ Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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AMELIA P. A. TRAVASSOS DA ROSA Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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HILDA GUZMAN Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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FANGLING XU Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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SHU-YUAN XIAO Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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VSEVOLOD L. POPOV Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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PEDRO F. C. VASCONCELOS Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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ROBERT B. TESH Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério de Saúde, Belem, Pará, Brazil; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

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Primary cultures of embryonic murine neurons and newborn mouse astrocytes were inoculated with West Nile virus (WNV) strain NY385-99 to compare the pathogenesis of WNV infection in these types of CNS cells. Two different outcomes were observed. WNV infection in the neurons was rapidly progressive and destructive; within 5 days, all of the neurons were destroyed through apoptosis. WNV infection in the astrocytes evolved more slowly and did not seem to be highly lethal to the cells. The infected astrocytes continued to produce infectious virus (104.6–106.5 PFU/mL) for 114 days, in a permissive, persistent infection. During this period, WNV antigen could be shown in the cytoplasm of the infected astrocytes by immunocytochemical assay, transmission electron microscopy of ultrathin sections, and in the cell culture medium by complement fixation test. Our results with this in vitro experimental murine cell model indicate that astrocytes can develop chronic or persistent infection with WNV, suggesting that these cells may play a role in the maintenance of WNV in the CNS.

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