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Am. J. Trop. Med. Hyg., 75(4), 2006, pp. 691-696
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

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

JOSE A. P. DINIZ, AMELIA P. A. TRAVASSOS DA ROSA, HILDA GUZMAN, FANGLING XU, SHU-YUAN XIAO, VSEVOLOD L. POPOV, PEDRO F. C. VASCONCELOS*, AND 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

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.

Received January 25, 2006. Accepted for publication June 1, 2006.

Acknowledgments: The authors thank Violet Han for expert assistance in electron microscopy.

Financial support: This work was supported in part by contracts NO1-AI25489 and NO1-AI30027 from the US National Institutes of Health.

* Address correspondence to Pedro Fernando de Costa Vasconcelos, Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saude, Av. Almirante Barroso, 492, 66090-000 Belem, PA, Brazil. E-mail: pedrovasconcelos{at}iec.pa.gov.br

Authors’ addresses: Jose A. P. Diniz and Pedro F. C. Vasconcelos, Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saù de. Ave. Almirante Barroso, 492, CEP 66093-020, Belém, Pará, Brasil, Telephone: +55 91 3202-4609, Fax: +55 91 3226-5262. Amelia P. A. Travassos Da Rosa, Hilda Guzman, Fangling Xu, Shu-Yuan Xiao, and Robert B. Tesh, Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, Telephone: 409-747-2431, Fax: 409-747-2429.






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Copyright © 2006 by the American Society of Tropical Medicine and Hygiene.