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Journal of Virology, September 2008, p. 9035-9042, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00674-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Common Marmosets (Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains{triangledown}

A. Paige Adams,1 Judith F. Aronson,1 Suzette D. Tardif,2 Jean L. Patterson,3 Kathleen M. Brasky,2 Robert Geiger,3 Melissa de la Garza,2 Ricardo Carrion Jr.,2,3 and Scott C. Weaver1*

Department of Pathology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas,1 Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, Texas,2 Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas3

Received 26 March 2008/ Accepted 1 July 2008

Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon. However, genetically and antigenically distinct strains from South America (SA) have seldom been associated with human disease or mortality despite serological evidence of infection. Because mice and other small rodents do not respond differently to the NA versus SA viruses like humans, we tested common marmosets (Callithrix jacchus) by using intranasal infection and monitoring for weight loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected animals either died or were euthanized on day 4 or 5 after infection due to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8 to 3.1 log10 PFU/ml on day 2 or 4 after infection, but there was no detectable viremia in the NA EEEV-infected animals. In contrast, virus was detected in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death. Similar to the brain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in the cerebral cortex with some perivascular hemorrhages. The findings of this study identify the common marmoset as a useful model of human EEE for testing antiviral drugs and vaccine candidates and highlight their potential for corroborating epidemiological evidence that some, if not all, SA EEEV strains are attenuated for humans.

* Corresponding author. Mailing address: University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0609. Phone: (409) 747-0758. Fax: (409) 747-2655. E-mail: sweaver{at}utmb.edu

{triangledown} Published ahead of print on 9 July 2008.

Journal of Virology, September 2008, p. 9035-9042, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00674-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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