Carrion Ricardo, Brasky Kathleen, Mansfield Keith, Johnson Curtis, Gonzales Monica, Ticer Anysha, Lukashevich Igor, Tardif Suzette, Patterson Jean
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.
J Virol. 2007 Jun;81(12):6482-90. doi: 10.1128/JVI.02876-06. Epub 2007 Apr 4.
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.
拉沙病毒每年在西非导致数千人死亡，被视为一种潜在的生物武器。为了建立拉沙热的小型非人灵长类动物模型，将拉沙病毒乔赛亚株皮下接种到普通狨猴体内。这种接种导致了一种全身性疾病，其临床和形态学特征与致命的人类拉沙病毒感染相似：发热、体重减轻、高病毒血症以及组织中的病毒RNA载量、肝酶升高，并且在第15天至20天之间出现严重发病情况。最显著的组织病理学发现包括多灶性肝坏死伴轻度炎症和肝细胞增殖、淋巴细胞耗竭以及间质性肾炎。肝细胞坏死区域的细胞聚集物主要由HAM56阳性巨噬细胞组成，缺乏CD3阳性和CD20阳性细胞，其特征是HLA-DP、DQ、DR染色强度明显降低。在淋巴结中也观察到主要组织相容性复合体II类表达明显降低。脾脏的免疫表型改变包括CD20阳性和CD3阳性细胞总数减少以及淋巴滤泡结构破坏。这些发现确定普通狨猴是人类拉沙热的合适模型，并提供了首个实验证据，表明拉沙病毒在组织中的复制与预期会损害适应性免疫的改变有关。
