Agol V I, Belov G A, Bienz K, Egger D, Kolesnikova M S, Raikhlin N T, Romanova L I, Smirnova E A, Tolskaya E A
M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow, Region 142782, Russia.
Virology. 1998 Dec 20;252(2):343-53. doi: 10.1006/viro.1998.9438.
The death of poliovirus-infected cells may occur in two forms: canonical cytopathic effect (CPE) (on productive infections) or apoptosis (when the viral reproduction is hindered by certain drugs or some other restrictive conditions). Morphological manifestations of the CPE and apoptosis, being distinct, share some traits (e.g., chromatin condensation and nuclear deformation). It was shown here that a permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (zVAD.fmk), prevented the development of the poliovirus-induced apoptosis on abortive infection. The apoptotic pathway could be dissected by an inhibitor of chymotrypsin-like serine proteases, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), which prevented the cleavage of DNA to oligonucleosome-sized pieces and nuclear fragmentation but did not suppress cellular shrinkage, cytoplasmic blebbing, and partial chromatin condensation. These results demonstrate that caspase activation is involved in the execution phase of the viral apoptosis and suggest that a nuclear subset of the apoptotic program is under a separate control, involving a TPCK-sensitive event. Neither zVAD.fmk nor TPCK, at the concentrations affecting the apoptotic response, exerted appreciable influence on the virus growth or cellular pathological changes on productive infection, indicating that the pathways leading to the poliovirus-evoked CPE and apoptosis are different.
典型细胞病变效应（CPE）（在增殖性感染时）或凋亡（当病毒复制受到某些药物或其他限制条件阻碍时）。CPE和凋亡的形态学表现虽不同，但有一些共同特征（如染色质浓缩和核变形）。此处研究表明，一种可渗透的半胱天冬酶抑制剂，苄氧羰基 - 缬氨酸 - 丙氨酸 - 天冬氨酸 - （甲氧基）氟甲基酮（zVAD.fmk），可阻止脊髓灰质炎病毒在顿挫感染时诱导的凋亡发展。凋亡途径可通过类胰凝乳蛋白酶样丝氨酸蛋白酶抑制剂N - 对甲苯磺酰 - L - 苯丙氨酸氯甲基酮（TPCK）进行剖析，该抑制剂可阻止DNA切割成寡核小体大小的片段以及核碎裂，但不抑制细胞收缩、细胞质起泡和部分染色质浓缩。这些结果表明，半胱天冬酶激活参与了病毒凋亡的执行阶段，并提示凋亡程序的一个核亚群受单独控制，涉及一个对TPCK敏感的事件。在影响凋亡反应的浓度下，zVAD.fmk和TPCK对病毒生长或增殖性感染时的细胞病理变化均无明显影响，这表明导致脊髓灰质炎病毒诱发的CPE和凋亡的途径是不同的。
