Rubenstein R, Price R W
Arch Virol. 1983;78(1-2):49-64. doi: 10.1007/BF01310858.
Replication of a thymidine kinase deficient (TK-) mutant of herpes simplex virus type 1 (HSV-1) was compared to replication of its parental TK+ strain in the PC 12 cell. This is a cell which ceases cell division and undergoes neuron-like morphological and physiological differentiation in the presence of nerve growth factor (NGF). No difference between mutant and parental strain replication was detected either when these cells were infected in the proliferative state or while maintained under the influence of NGF. Neither viral TK nor enhanced cellular TK activity was detected during TK- HSV-1 replication, which proceeded in the presence of selective antiviral drugs that inhibited TK+ HSV-1 viral replication. Moreover, thymidylate synthetase was inhibited early in TK- infection, and reutilization of thymine nucleotides derived from degraded cellular DNA was not detected. Under the conditions of these in vitro studies, increased production of dTTP as a result of enhanced TK activity did not appear to be rate-limiting, despite the non-dividing "differentiated" state of the PC 12 cell.
将单纯疱疹病毒1型（HSV-1）的胸苷激酶缺陷型（TK-）突变体的复制与其亲代TK+毒株在PC 12细胞中的复制进行了比较。PC 12细胞在神经生长因子（NGF）存在的情况下会停止细胞分裂，并经历神经元样的形态和生理分化。当这些细胞在增殖状态下被感染或在NGF的影响下维持时，未检测到突变体和亲代毒株复制之间的差异。在TK-HSV-1复制过程中，未检测到病毒胸苷激酶或增强的细胞胸苷激酶活性，该复制过程在抑制TK+ HSV-1病毒复制的选择性抗病毒药物存在的情况下进行。此外，在TK-感染早期胸苷酸合成酶受到抑制，并且未检测到源自降解的细胞DNA的胸腺嘧啶核苷酸的再利用。在这些体外研究的条件下，尽管PC 12细胞处于非分裂的“分化”状态，但由于胸苷激酶活性增强导致的dTTP产量增加似乎不是限速因素。
