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Journal of Virology, June 2007, p. 6482-6490, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.02876-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Lassa Virus Infection in Experimentally Infected Marmosets: Liver Pathology and Immunophenotypic Alterations in Target Tissues

Ricardo Carrion Jr.,¹ Kathleen Brasky,² Keith Mansfield,³ Curtis Johnson,¹ Monica Gonzales,¹ Anysha Ticer,¹ Igor Lukashevich,⁴ Suzette Tardif,^2, and Jean Patterson^1*

Department of Virology and Immunology,¹ Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227,² New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,³ Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201⁴

Received 28 December 2006/ Accepted 28 March 2007

Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

Published ahead of print on 4 April 2007.

Present address: Sam and Ann Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229.