FRIEND VIRUS SUSCEPTIBILITY IN YOUNG AND AGED MICE

年轻和老年小鼠的朋友病毒易感性

• 批准号: 3422518
• 负责人: DENEEN STEWART
• 金额: $ 0.92万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3422518
• 关键词: Friend virus; RNA directed DNA polymerase; age difference; cell type; flow cytometry; gene expression; immunologic assay /test; in situ hybridization; laboratory mouse; northern blottings; pathologic process; splenomegaly; virus replication; western blottings

Friend virus (FV) causes erythroleukemia and immunosuppression in susceptible mouse strains. Many studies have examined FV induced suppression of both humoral and cellular immunity. However, few studies have focused on differences in disease development in young and aged mice. This study will establish the differences in susceptibility between young and aged mice and determine the mechanism for this age related difference. Specifically I will: 1. Confirm our observation that FV induced disease is decreased in aged versus young mice. This will be accomplished by determining the degree of splenomegaly. 2. Examine difference in viral replication and expression of FV in target organsof young and aged mice. Replication of herpes virus will be determined by x c assay, of spleen focus forming virus by enumerating spleen foci, and total virus expression by reverse transcriptase activity. Virus expression will be further explored using Western and Northern blot analysis to examine specific viral products. 3. Determine if there are age related differences in the number of target cells, range of target cells, or the ability of target cells to sustain a viral infection using flow cytometry to detect changes in cell type and number and in situ hybridization to detect viral replication. Further, host gene loci have been demonstrated to alter FV replication and disease changes in erythroprotein receptor and C-kit will be examined by antibody techniques, Northern analysis and, if necessary, DNA sequencing maturation, changes in these loci can lead to changes in cell development. Therefore, loci that effect FV susceptibility or receptors that are regulated by the loci will be examined. Friend virus in an aging mouse model is an excellent system to gain information on how other retroviruses with similar life cycles replicate in young verses aged animals .and will give new insights regarding approaches to human HIV studies.

弗兰德病毒 (FV) 会导致红白血病和免疫抑制 易感小鼠品系。 许多研究已经检验了 FV 诱导的 抑制体液免疫和细胞免疫。 但很少有研究 重点关注年轻人和老年人疾病发展的差异 老鼠。 这项研究将确定敏感性差异 在年轻和老年小鼠之间进行比较并确定该年龄的机制 相关差异。 具体来说我会： 1. 证实我们的观察结果，即 FV 诱发的疾病在老年人中减少 与年轻小鼠相比。这将通过确定程度来完成 脾肿大。 2. 检查目标中病毒复制和 FV 表达的差异 年轻和年老小鼠的器官。 疱疹病毒的复制 通过 x c 测定，通过计数确定脾病灶形成病毒 脾病灶和逆转录酶的总病毒表达 活动。 将使用西方和 Northern 印迹分析用于检查特定的病毒产物。 3. 确定目标数量是否存在年龄相关差异 细胞、靶细胞的范围或靶细胞维持的能力 使用流式细胞术检测病毒感染的细胞类型的变化和 数量和原位杂交来检测病毒复制。 此外，宿主基因位点已被证明可以改变 FV 复制 并检查红蛋白受体和C-kit的疾病变化 通过抗体技术、Northern 分析以及必要时的 DNA 测序成熟时，这些位点的变化会导致细胞的变化 发展。 因此，影响 FV 敏感性或受体的位点 将检查由基因座调节的那些。 衰老小鼠模型中的 Friend 病毒是获得 有关具有相似生命周期的其他逆转录病毒如何复制的信息 在年轻的诗句中，老年的动物。并将给出关于 人类艾滋病毒研究的方法。