Earl P L, Moss B, Morrison R P, Wehrly K, Nishio J, Chesebro B
Science. 1986 Nov 7;234(4777):728-31. doi: 10.1126/science.3490689.
The current prevalence of the acquired immune deficiency syndrome in humans has provoked renewed interest in methods of protective immunization against retrovirus-induced diseases. In this study, a vaccinia-retrovirus recombinant vector was constructed to study mechanisms of immune protection against Friend virus leukemia in mice. The envelope (env) gene from Friend murine leukemia virus (F-MuLV) was inserted into the genome of a vaccinia virus expression vector. Infected cells synthesized gp85, the glycosylated primary product of the env gene. Processing to gp70 and p15E, and cell surface localization, were similar to that occurring in cells infected with F-MuLV. Mice inoculated with live recombinant vaccinia virus had an envelope-specific T-cell proliferative response and, after challenge with Friend virus complex, developed neutralizing antibody and cytotoxic T cells (CTL) and were protected against leukemia. In contrast, unimmunized and control groups developed a delayed neutralizing antibody response, but no detectable CTL, and succumbed to leukemia. Genes of the major histocompatibility complex influenced protection induced by the vaccinia recombinant but not that induced by attenuated N-tropic Friend virus.
目前人类获得性免疫缺陷综合征的流行情况引发了人们对针对逆转录病毒诱导疾病的保护性免疫方法的新兴趣。在本研究中,构建了一种痘苗 - 逆转录病毒重组载体,以研究小鼠抗弗氏病毒白血病的免疫保护机制。将来自弗氏小鼠白血病病毒(F - MuLV)的包膜(env)基因插入痘苗病毒表达载体的基因组中。受感染的细胞合成了env基因的糖基化初级产物gp85。加工成gp70和p15E以及细胞表面定位与感染F - MuLV的细胞中发生的情况相似。接种活重组痘苗病毒的小鼠具有包膜特异性T细胞增殖反应,在用弗氏病毒复合物攻击后,产生中和抗体和细胞毒性T细胞(CTL),并受到白血病的保护。相比之下,未免疫组和对照组产生延迟的中和抗体反应,但未检测到CTL,并死于白血病。主要组织相容性复合体的基因影响痘苗重组体诱导的保护作用,但不影响减毒N - 嗜性弗氏病毒诱导的保护作用。