Multi-stage Friend murine erythroleukemia: molecular insights into oncogenic cooperation

Friend retroviruses and Friend disease have provided powerful experimental tools in the fields of virology and oncology. During the nineteen-seventies, they have been of great importance in understanding the mechanisms of resistance of mice to retroviral infection, leading to the identification of several host genes that affect Friend virus replication in target cells and control host immune response to the viral antigens [1,2]. Recent advances made in primates retroviral restriction activities have given major relevance to the previously accrued murine data[3,4]. For example, the retroviral restriction factor Fv1 (Friend virus susceptibility factor 1) [5-8] provides resistance to infection by particular murine leukemia viruses, and the Ref1/Lv1/TRIM5 factor mediates resistance to diverse retroviruses in primates, including humans [9-11]. These mechanisms of resistance target a common capsid molecular determinant [12,13]. Remarkably, the murine gene Rfv3 (Recovery from Friend virus 3) which influences Friend viremia [14] and retroviral neutralizing antibody responses [15] encodes APOBEC3 known otherwise as a powerful antiretroviral factor that restricts retroviral virions of cognate origin [16-19]. Moreover, the erythroleukemia induced in mice by Friend retroviruses represent experimental neoplasms that have been valuable for characterizing the multi-stage progression of leukemia, for identifying oncogenes or tumor suppressor genes involved during this process, for understanding the contribution of host genes to cancer, and for investigating the mechanisms leading to cell growth autonomy. The purpose of this review is to highlight the important insights that have arisen from the studies on the Friend disease and to discuss the molecular events involved in the outgrowth of preleukemic cells and their progression to malignancy.Friend acute erythroleukemias are caused in susceptible mice by various strains of Friend leukemia viruses (FLV). The description of the initia