Hasenkrug K J, Brooks D M, Robertson M N, Srinivas R V, Chesebro B
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institute of Health, 903 South 4th Street, Hamilton, Montana, 59840, USA.
Virology. 1998 Aug 15;248(1):66-73. doi: 10.1006/viro.1998.9264.
Several immunological epitopes are known to be located within the Friend murine leukemia virus (F-MuLV) envelope protein, but their relative contributions to protection from Friend virus-induced disease are not known. To determine how expression of various immunological determinants affected protection, mice were immunized with recombinant vaccinia viruses expressing different portions of the F-MuLV envelope protein, and they were then challenged with a lethal dose of Friend virus complex. The disease parameters that were followed in the mice were early viremia, early splenomegaly, and late splenomegaly. Both the N-terminal and C-terminal portions of the F-MuLV gp70 were found to protect against late splenomegaly, the primary clinical sign associated with virus-induced erythroleukemia. However, neither region alone protected against early splenomegaly and early viremia, indicating poor immunological control over early virus replication and spread through the spleen and blood. In contrast, mice immunized with a vaccine expressing the entire F-MuLV envelope protein were protected against all three disease parameters. The results indicated that expression of multiple immunological determinants including both T-helper and B cell epitopes was necessary for full protection.
已知几个免疫表位位于弗瑞德鼠白血病病毒(F-MuLV)包膜蛋白内,但它们对预防弗瑞德病毒所致疾病的相对作用尚不清楚。为了确定各种免疫决定簇的表达如何影响保护作用,用表达F-MuLV包膜蛋白不同部分的重组痘苗病毒免疫小鼠,然后用致死剂量的弗瑞德病毒复合物攻击它们。在小鼠中监测的疾病参数为早期病毒血症、早期脾肿大和晚期脾肿大。发现F-MuLV gp70的N端和C端部分均可预防晚期脾肿大,这是与病毒诱导的红白血病相关的主要临床体征。然而,单独一个区域均不能预防早期脾肿大和早期病毒血症,这表明对早期病毒复制以及通过脾脏和血液传播的免疫控制较差。相比之下,用表达完整F-MuLV包膜蛋白的疫苗免疫的小鼠对所有三个疾病参数均有保护作用。结果表明,包括T辅助细胞和B细胞表位在内的多个免疫决定簇的表达对于全面保护是必要的。