title: Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues.
abstract: 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.
authors.affiliation: Department of Virology and Immunology, Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245-0549, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carrion
authors.forename: Kathleen
authors.initials: K
authors.lastname: Brasky
authors.forename: Keith
authors.initials: K
authors.lastname: Mansfield
authors.forename: Curtis
authors.initials: C
authors.lastname: Johnson
authors.forename: Monica
authors.initials: M
authors.lastname: Gonzales
authors.forename: Anysha
authors.initials: A
authors.lastname: Ticer
authors.forename: Igor
authors.initials: I
authors.lastname: Lukashevich
authors.forename: Suzette
authors.initials: S
authors.lastname: Tardif
authors.forename: Jean
authors.initials: J
authors.lastname: Patterson
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D002144:Callithrix / Q000821:virology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007249:Inflammation; D007835:Lassa Fever / Q000473:pathology / Q000821:virology*; D007836:Lassa virus / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D008214:Lymphocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: D018951:Antigens, CD20; D017252:CD3 Complex