MECHANISMS OF PATHOGENESIS AND RECOVERY IN FRIEND RETROVIRUS-INDUCED LEUKEMIA

FRIEND逆转录病毒引起的白血病的发病机制和恢复机制

• 批准号: 3746454
• 负责人: B W CHESEBRO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746454
• 关键词: Friend leukemia; Friend virus; MHC class I antigen; gene induction /repression; genetic strain; heterozygote; host organism interaction; immune response genes; immunity; immunogenetics; immunoglobulin G; immunosuppression; laboratory mouse; major histocompatibility complex; microorganism immunology; molecular oncology; neoplasm /cancer genetics; neoplasm /cancer immunology; neutralizing antibody; viral vaccines; virulence; virus antigen; virus envelope; virus genetics; virus infection mechanism; virus load; virus protein; virus related neoplasm /cancer

Friend virus (FV) is a complex of 2 mouse retroviruses which induce rapid erythroleukemia in many strains of adult mice. Various genes in susceptible mice can modify the outcome of FV infection. Our laboratory has identified 5 such genes including 4 major histocompatibility complex (MHC) regions (D, IA, IE and T) and one non-MHC gene, Rfv-3. These genes all influence the host immune response to FV and FV leukemia cells and can even induce spontaneous recovery from leukemia or facilitate successful protective vaccination against challenge with live FV or FV leukemia cells. This years work studied the mechanism of the influence of the MHC D region on recovery. Using mice expressing only one allele of the beta2- microglobulin gene caused a 50% reduction in the expression of the MHC D region gene product. However this did not reduce the incidence of recovery from FV leukemia indicating that heterozygous levels of the D/b allele are adequate for recovery. The results suggest that the non- recovery D/d allele or the closely linked L/d allele might cause a negative influence on the recovery process. The MHC IE region was also studied in this system, and it was found to exert both a positive and a negative influence on recovery from leukemia. The positive affect was due to the role of the E molecule on presentation of FV envelope protein antigens to the immune system. The negative effect appeared to act by its influence on selection of T cell subsets during ontogeny.

Friend病毒（FV）是由两种小鼠逆转录病毒组成的复合体， 红白血病在许多品系的成年小鼠。 中各种基因 易感小鼠可以改变FV感染的结果。 本实验室 已经鉴定了5个这样的基因，包括4个主要组织相容性复合体 (MHC)区域（D、IA、IE和T）和一个非MHC基因Rfv-3。 这些基因 都影响宿主对FV和FV白血病细胞的免疫应答， 甚至可以诱导白血病的自发恢复， 针对活FV或FV攻击的成功保护性疫苗接种 白血病细胞 近年来的研究工作主要是探讨MHC D基因对细胞增殖的影响机制 地区复苏。 使用只表达β 2- 微球蛋白基因导致MHC表达减少50%， D区基因产物。 然而，这并没有减少 从FV白血病的恢复表明D/B的杂合水平 等位基因足以恢复。 结果表明，非 恢复性D/d等位基因或紧密连锁的L/d等位基因可能导致 对复苏进程产生负面影响。 在该系统中还研究了MHC IE区，发现其 对白血病的康复既有积极的影响，也有消极的影响。 这种积极的影响是由于E分子在呈递中的作用 的FV包膜蛋白抗原的免疫系统。 负 作用似乎是通过其对T细胞亚群选择的影响而起作用的 在个体发育过程中。