Helper virus is not required for in vitro erythroid transformation of hematopoietic cells by Friend virus.
Helper virus is not required for in vitro erythroid transformation of hematopoietic cells by Friend virus.
复制标题
弗兰德病毒对造血细胞进行体外红系转化不需要辅助病毒。
DOI：
10.1073/pnas.77.9.5287
复制
发表时间：
1980
影响因子：
11.1
通讯作者：
Krantz,SB
中科院分区：
文献类型：
--
作者：
Hankins,WD;Krantz,SB
Friend多核细胞增多症病毒复合体(FVP)由复制缺陷的脾病灶形成病毒(SFFV)和辅助性Friend小鼠白血病病毒(MuLV-F)组成，在体内2-3周内产生红白血病。我们最近报道了用FVP体外转化骨髓细胞，在感染后4-6天产生成簇的红系集落(红系破裂)。与未感染的骨髓细胞相比，FVP处理的细胞在没有添加促红细胞生成素的情况下增殖和分化(合成血红蛋白)，促红细胞生成素是红细胞生成的生理调节因素。辅助小鼠白血病病毒(MuLV)和SFFV在体外红系转化中的相对作用已被研究。假类型研究和克隆的MuLV-F(不含SFFV)不能诱导猝发的发现表明，SFFV对FvP的这种体外效应是必不可少的。由于SFFV不能在没有辅助MULV的情况下获得，我们通过辅助缺乏和辅助过剩FVP制备的动力学分析来评估转化过程中对MULV的需求。而辅助剂过量的FvP在体内和体外都具有单次打击动力学，而辅助剂缺乏的FvP在体内滴定形成脾病灶时遵循多击打动力学。在注射前将MuLV-F加入缺乏辅助者的FVP中，可显著增强脾病灶的形成，并使多次击打动力学转变为单次击打动力学。相反，在体外滴定相同的制剂用于红系爆裂转化时，产生一次击打动力学，而添加辅助剂MuLV-F则没有影响。加或不加MuLV-F后，爆发期的时间进程相似。与爆发式转化不同，这些受感染的培养物生产SFFV遵循多次击打动力学。在感染时加入MuLV-F可促进SFFV的产生，并将滴定曲线从多次击打转换为一次击打。这些数据与SFFV在体外有能力进行红系转化的观点是一致的，但需要辅助MuLV进行复制。
The Friend polycythemia virus complex (FVP), consisting of the replication-defective spleen focus-forming virus (SFFV) and a helper Friend murine leukemia virus (MuLV-F), produces erythroleukemia within 2-3 weeksin vivo. We have recently reportedin vitrotransformation of bone marrow cells by FVP, producing clusters of erythroid colonies (erythroid bursts) 4-6 days after infection. In contrast to uninfected bone marrow cells, FVP-treated cells proliferated and differentiated (synthesized hemoglobin) in the absence of added erythropoietin, the physiologic regulator of erythropoiesis. The relative roles of helper murine leukemia virus (MuLV) and SFFV in thein vitroerythroid transformation have now been examined. Pseudotype studies and the finding that cloned MuLV-F (free of SFFV) did not induce burst formation indicated that SFFV was essential for thisin vitroeffect of FVP. Because SFFV could not be obtained free of helper MuLV, we assessed the requirement of MuLV in the transformation by kinetic analyses of helper-deficient and helper-excess FVP preparations. Whereas helper-excess FVP gave single-hit kinetics bothin vivoandin vitro, the helper-deficient FVP followed multiple-hit kinetics when titrated for spleen focus formationin vivo. Addition of MuLV-F to helper-deficient FVP prior to injection resulted in a marked enhancement of spleen focus formation and a conversion from multiple-hit to single-hit kinetics. In contrast, titration of this same preparation for erythroid burst transformationin vitroyielded single-hit kinetics, and the addition of helper MuLV-F had no effect. The time course of burst development was similar with or without added MuLV-F. Unlike burst transformation, SFFV production by these infected cultures followed multiple-hit kinetics. Addition of MuLV-F at the time of infection led to an enhancement of SFFV production and conversion of the titration curve from multiple-hit to single-hit. These data are consistent with the idea that SFFV is competent for erythroid transformationin vitro, but requires helper MuLV for its replication.