Poast Joyce, Seidel H Martin, Hendricks Michelle D, Haslam Jennifer A, Levy Hilton B, Baron Samuel
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-1019, USA.
J Interferon Cytokine Res. 2002 Oct;22(10):1035-40. doi: 10.1089/107999002760624260.
Induction of a large number of the components of the interferon (IFN) system (IFN genes, their mRNAs, IFN proteins, IFN receptors, IFN signaling molecules, the IFN response genes, and their effector proteins) has been studied. Less well studied is the comparative induction of these components in vivo. Induction of IFN by double-stranded RNA (dsRNA) treatment mimics certain aspects of viral infection and induces the components of the IFN system. To determine the comparative sensitivity of detection of induction in mice, we initially studied the limiting concentrations of polyribinosinic-polyribocytidylic acid, polylysine complex (poly I:CLC, a synthetic dsRNA preparation), for induction of four representative components of the IFN system: (1) IFN in serum, (2) the IFN response gene mRNA ISG54 in spleen and liver, (3) the IFN-beta mRNA in spleen, and (4) resistance of mice to Banzi viral infection. The results of this initial study showed that resistance to infection was 7-fold more sensitive for detection of the IFN response than was ISG54 mRNA and 70-fold more sensitive than either IFN-beta mRNA or IFN production in serum. In comparison, mouse cells in vitro treated with poly I:CLC were 3-10-fold less sensitive to its antiviral action than is the mouse. The results demonstrate that in the four tests in mice, the most sensitive indicator of poly I:CLC induction of the IFN system was protection against Banzi viral infection, followed by ISG54 mRNA levels, IFN-beta mRNA, and IFN protein levels. It is hypothesized that the highest sensitivity of mouse protection may be due to priming by the initial poly I:CLC-induced IFN of the subsequent Banzi virus-induced IFN, resulting in rapid and high concentrations of IFN at the local site of viral replication. Future studies are needed to study other molecular components of the IFN system to identify those that cause the unanticipated high sensitivity of mice to protection against Banzi virus.
人们已经对大量干扰素（IFN）系统的组成成分（IFN基因、其mRNA、IFN蛋白、IFN受体、IFN信号分子、IFN反应基因及其效应蛋白）的诱导情况进行了研究。而对这些成分在体内的比较诱导情况的研究则较少。双链RNA（dsRNA）处理诱导IFN可模拟病毒感染的某些方面，并诱导IFN系统的组成成分。为了确定小鼠中诱导检测的比较敏感性，我们最初研究了聚肌苷酸-聚胞苷酸、聚赖氨酸复合物（poly I:CLC，一种合成的dsRNA制剂）诱导IFN系统四个代表性成分的极限浓度：（1）血清中的IFN，（2）脾脏和肝脏中IFN反应基因mRNA ISG54，（3）脾脏中的IFN-β mRNA，以及（4）小鼠对班齐病毒感染的抵抗力。这项初步研究的结果表明，对感染的抵抗力检测IFN反应的敏感性比ISG54 mRNA高7倍，比血清中的IFN-β mRNA或IFN产生高70倍。相比之下，体外经poly I:CLC处理的小鼠细胞对其抗病毒作用的敏感性比小鼠低3至10倍。结果表明，在小鼠的四项检测中，poly I:CLC诱导IFN系统的最敏感指标是对班齐病毒感染的保护作用，其次是ISG54 mRNA水平、IFN-β mRNA和IFN蛋白水平。据推测，小鼠保护作用的最高敏感性可能是由于最初poly I:CLC诱导的IFN对随后班齐病毒诱导的IFN进行了预激发，导致在病毒复制局部部位迅速产生高浓度的IFN。未来需要开展研究以研究IFN系统的其他分子成分，从而确定那些导致小鼠对班齐病毒保护作用出现意外高敏感性的成分。
