Shoemaker Megan L, Smirnova Natalia P, Bielefeldt-Ohmann Helle, Austin Kathleen J, van Olphen Alberto, Clapper Jeffrey A, Hansen Thomas R
Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, Colorado 80523, USA.
J Interferon Cytokine Res. 2009 Jan;29(1):23-35. doi: 10.1089/jir.2008.0033.
Persistent infection with bovine viral diarrhea virus (BVDV) serves as a reservoir for the perpetuation of infection in cattle populations and causes a range of adverse effects on the health of the host. To study the interactions of the virus with the host, gene expression was compared in the blood of persistently infected (PI) and uninfected steer, and in the blood and tissues of PI fetuses, transiently infected (TI), and uninfected bovine fetuses. Microarray analysis of PI steer blood revealed differential gene expression indicative of an interferon (IFN) response including genes involved in cell cycle regulation, which may contribute to long-term adverse effects. Upregulation of IFN-stimulated genes (e.g., ISG15, PKR) and RNA helicases (RIG-I, LGP2, MDA-5) was identified in both PI fetal and steer blood in comparison to controls, indicating a continued stimulation of the innate antiviral response as a result of the persistent viremia. ISG15 was studied in further detail, implicating reticular cells as basal producers of ISG15 in the spleen, in addition to endothelial and macrophage-like cells in infected spleen. Consequences of chronic IFN pathway activation in PI cattle may include growth- and immunosuppression, the pathogenesis of which is still poorly understood. This study lends new insights into the interactions between BVDV and its host, and can serve as a model for studies of the role of the IFN system in persistent infections.
牛病毒性腹泻病毒（BVDV）的持续感染是牛群中感染持续存在的一个源头，并对宿主健康造成一系列不利影响。为了研究该病毒与宿主的相互作用，对持续感染（PI）和未感染的公牛血液，以及PI胎儿、短暂感染（TI）和未感染的牛胎儿的血液及组织中的基因表达进行了比较。对PI公牛血液的微阵列分析揭示了差异基因表达，表明存在干扰素（IFN）反应，包括参与细胞周期调控的基因，这可能导致长期的不利影响。与对照相比，在PI胎儿和公牛血液中均鉴定出IFN刺激基因（如ISG15、PKR）和RNA解旋酶（RIG-I、LGP2、MDA-5）的上调，表明由于持续病毒血症，先天性抗病毒反应持续受到刺激。对ISG15进行了更详细的研究，结果表明，除了感染脾脏中的内皮细胞和巨噬样细胞外，网状细胞也是脾脏中ISG15的基础生产者。PI牛慢性IFN途径激活的后果可能包括生长抑制和免疫抑制，其发病机制仍知之甚少。本研究为BVDV与其宿主之间的相互作用提供了新的见解，并可作为研究IFN系统在持续感染中作用的模型。
