Lee Sang-Ryul, Nanduri Bindu, Pharr G Todd, Stokes John V, Pinchuk Lesya M
Department of Basic Science, Mississippi State University, Mississippi State, MS 39762-6100, USA.
Biochim Biophys Acta. 2009 Jan;1794(1):14-22. doi: 10.1016/j.bbapap.2008.09.005. Epub 2008 Sep 30.
The complete annotation of the cattle genome allows reliable protein identification by tandem mass spectrometry (MS(2)) and greatly facilitates proteomics. Previously, we reported that differential detergent fractionation (DDF) analysis of bovine monocytes reveals proteins related to antigen pattern recognition, uptake and presentation to immunocompetent lymphocytes. Here we have identified 47 bovine proteins, involved in immune function of professional antigen-presenting cells (APC) that have been significantly altered after cytopathic (cp) Bovine Viral Diarrhea Virus (BVDV) infection. In particular, proteins related to immune responses such as cell adhesion, apoptosis, antigen uptake, processing and presentation, acute phase response proteins, MHC class I- and II-related proteins and other molecules involved in immune function of professional antigen presentation have been significantly altered after BVDV infection. Our data suggest that cp BVDV, while promoting monocyte activation and differentiation, is inhibiting their antigen presentation to immunocompetent T cells, thus resulting in the uncontrolled inflammation mediated by activated macrophages, enhanced viral spread, and impaired anti-viral defense mechanisms in the host.
牛基因组的完整注释使得通过串联质谱法(MS(2))进行可靠的蛋白质鉴定成为可能,并极大地促进了蛋白质组学研究。此前,我们报道过对牛单核细胞进行差异去污剂分级分离(DDF)分析可揭示与抗原模式识别、摄取以及呈递给免疫活性淋巴细胞相关的蛋白质。在此,我们鉴定出了47种牛蛋白质,它们参与专职抗原呈递细胞(APC)的免疫功能,在细胞病变型(cp)牛病毒性腹泻病毒(BVDV)感染后发生了显著变化。特别是,与免疫反应相关的蛋白质,如细胞黏附、凋亡、抗原摄取、加工和呈递、急性期反应蛋白、MHC I类和II类相关蛋白以及其他参与专职抗原呈递免疫功能的分子,在BVDV感染后均发生了显著变化。我们的数据表明,cp BVDV在促进单核细胞活化和分化的同时,抑制了它们向免疫活性T细胞的抗原呈递,从而导致由活化巨噬细胞介导的不受控制的炎症、病毒传播增强以及宿主抗病毒防御机制受损。