Cheung S C, Chattopadhyay S K, Morse H C, Pitha P M
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Virol. 1991 Feb;65(2):823-8. doi: 10.1128/JVI.65.2.823-828.1991.
A syndrome characterized by severe immunodeficiency and lymphoproliferation develops in susceptible strains of mice infected with a mixture of murine leukemia viruses (MuLVs) designated LP-BM5 MuLV. The etiologic agent in this mixture has been shown to be a replication-defective virus (BM5d) with a 4.8-kb genome that required replication-competent helper viruses, primarily ecotropic (BM5e), for cell-to-cell spread in the host. In the present study, we studied the expression of BM5d and BM5e in tissues of infected mice at various times after inoculation in relation to the expression of cytokine genes that may contribute to the pathogenesis of this disorder. Northern (RNA) analysis of total RNA showed that BM5d was expressed at significant levels in lymphoid tissues within 1 week of infection and that the levels of expression increased with time after inoculation. By 16 weeks postinfection, BM5d was expressed in all tissues examined. Expression of BM5e was relatively more restricted to lymphoid tissues and was detected at lower levels than expression of BM5d at early times after infection, but this virus was expressed in all tissues by 16 weeks. Infection with the virus mixture was associated with constitutive expression of tumor necrosis factor in all tissues examined and of interleukin-1 (IL-1) in lymphoid tissues within 1 week of infection, and at later times with widespread expression of these cytokines and gamma interferon. Also, the levels of interferon regulatory factor 1 mRNA were significantly increased in all infected tissues during the infection. In contrast, expression of IL-3, IL-4, IL-5, and IL-6 was not detectable by Northern analysis of the respective mRNAs in any infected tissue at early or late times postinfection.
感染了名为LP - BM5 MuLV的鼠白血病病毒混合物的易感小鼠品系会出现一种以严重免疫缺陷和淋巴细胞增殖为特征的综合征。已证明该混合物中的病原体是一种复制缺陷型病毒（BM5d），其基因组为4.8 kb，在宿主中进行细胞间传播时需要有复制能力的辅助病毒，主要是嗜亲性病毒（BM5e）。在本研究中，我们研究了接种后不同时间感染小鼠组织中BM5d和BM5e的表达情况，以及可能与这种疾病发病机制有关的细胞因子基因的表达情况。对总RNA进行的Northern（RNA）分析表明，感染后1周内，BM5d在淋巴组织中大量表达，且接种后表达水平随时间增加。感染后16周时，BM5d在所有检测组织中均有表达。BM5e的表达相对更局限于淋巴组织，在感染后早期检测到的水平低于BM5d的表达，但到16周时该病毒在所有组织中均有表达。感染病毒混合物与所有检测组织中肿瘤坏死因子的组成性表达以及感染后1周内淋巴组织中白细胞介素 - 1（IL - 1）的表达有关，在后期这些细胞因子和γ干扰素广泛表达。此外，感染期间所有感染组织中干扰素调节因子1 mRNA的水平均显著增加。相比之下，感染后早期或晚期，通过对相应mRNA进行Northern分析，在任何感染组织中均未检测到IL - 3、IL - 4、IL - 5和IL - 6的表达。
