Jolly D J, Willis R C, Friedmann T
Mol Cell Biol. 1986 Apr;6(4):1141-7. doi: 10.1128/mcb.6.4.1141-1147.1986.
Human lymphoblasts deficient in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) were infected with an amphotropic helper-free retroviral vector expressing human HPRT cDNA. The stability and expression of the HPRT provirus in five cell lines with different proviral integration sites were examined by determining HPRT mutation and reversion frequencies and by blot hybridization studies. Mutation to the HPRT-negative phenotype occurred at frequencies of approximately 4 X 10(-5) to 3 X 10(-6) per generation. Most mutations in each of the five cell lines were associated with partial or complete deletions or rearrangements of the provirus. Several mutants retained a grossly intact HPRT provirus, and in one such mutant HPRT shutdown resulted from a revertible epigenetic mechanism that was not associated with global changes in proviral methylation. Therefore, mutation and shutdown of the HPRT provirus in human lymphoblasts result from mechanisms similar to those reported for several other avian and mammalian replication-competent retroviruses.
用表达人次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HPRT）cDNA的嗜双性无辅助病毒逆转录载体感染缺乏该酶的人淋巴母细胞。通过测定HPRT突变和回复频率以及印迹杂交研究，检测了五个具有不同前病毒整合位点的细胞系中HPRT前病毒的稳定性和表达。向HPRT阴性表型的突变发生频率约为每代4×10^(-5)至3×10^(-6)。五个细胞系中每个细胞系的大多数突变都与前病毒的部分或完全缺失或重排有关。几个突变体保留了大致完整的HPRT前病毒，在一个这样的突变体中，HPRT关闭是由一种可逆的表观遗传机制导致的，该机制与前病毒甲基化的全局变化无关。因此，人淋巴母细胞中HPRT前病毒的突变和关闭是由与其他几种有复制能力的禽和哺乳动物逆转录病毒所报道的机制类似的机制引起的。
