BIOLOGICAL AND PHYSICAL PROPERTIES OF FRIEND VIRUS

朋友病毒的生物学和物理特性

• 批准号: 3179008
• 负责人: ROBERT J ECKNER
• 金额: $ 19.44万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179008
• 关键词: B lymphocyte; Friend virus; bone marrow transplantation; cell growth regulation; clone cells; density gradient ultracentrifugation; erythroleukemia; hematopoietic stem cells; host neoplasm interaction; immunofluorescence technique; latent virus infection; leukopoiesis; neoplasm /cancer immunology; oncogenes; radiation leukemia; viral leukemogenesis; virus assembly; virus cytopathogenic effect; virus genetics; virus replication

The overall objective of this project is to determine if defective Friend spleen focus-forming virus (SFFV) carries genetic information which is able to function as a hemopoietic self-renewal gene when introduced into the pluripotent hemoietic stem cell (CFU-S) of murine bone marrow cells. Major Specific Aims; SFFV constructions. To construct a transmissible retrovirus consisting of the molecularly cloned Friend SFFV and an altered mouse dihydrofolate reductase (dhfr) sequence. The presence of a single mutant dhfr sequence serves as a dominant-acting selectable gene. Persistence if engineered defective SFFV. Suspensions of murine bone marrow cells enriched for CFU-S will be exposed to infectious SFFV-dhfr to determine if the host range of this engineered, defective virus includes hemopoietic cells. Virus-treated marrow will be injected into lethally-irradaited histocompatible adult recipients. These mice will be monitored for latent SFFV persistence. SFFV and stem cells self-renewal. Using donor marrow which are predominantly SFFV+ CFU-S, to probe for SFFV-induced alterations in host hematopoiesis and stem cell renewal. SFFV+ marrow cells will be retrieved from latently infected mice and serially transplanted to determine their ability to self-renew and protect or rescue lethally-irradiated recipients from total hemopoietic failure and death. To insure repopulation by predominantly SFFV+ CFU-S, we shall treat reconstituted mice with a drug regimen if methotrexate (Mtx). Identify of an SFFV self-renewal gene. To determine if the envelope (env) sequences which encode gp52sfv are required for the induction of extended CFU-S self renewal. A number of well-defined SFFV insertion-deletion mutants will be reconstituted with dhfr, pseudotypes with helper, and used to infect CFU-S. Latent persistence will be confirmed using an SFFV representative probe, while the SFFV+ stem cells will be monitored for self-renewal capacity via serial transplantation into lethally irradiated syngeneic adult mice. Vector transfer of self-renewal may eventually be exploited to the benefit of the host whether he/she be suffering from an aquired or congenital defect in hemopoiesis erytghromyeloid and lymphoid.

该项目的总体目标是确定是否有缺陷的朋友