Nogal M L, González de Buitrago G, Rodríguez C, Cubelos B, Carrascosa A L, Salas M L, Revilla Y
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
J Virol. 2001 Mar;75(6):2535-43. doi: 10.1128/JVI.75.6.2535-2543.2001.
African swine fever virus (ASFV) A224L is a member of the inhibitor of apoptosis protein (IAP) family. We have investigated the antiapoptotic function of the viral IAP both in stably transfected cells and in ASFV-infected cells. A224L was able to substantially inhibit caspase activity and cell death induced by treatment with tumor necrosis factor alpha and cycloheximide or staurosporine when overexpressed in Vero cells by gene transfection. We have also observed that ASFV infection induces caspase activation and apoptosis in Vero cells. Furthermore, using a deletion mutant of ASFV lacking the A224L gene, we have shown that the viral IAP modulates the proteolytic processing of the effector cell death protease caspase-3 and the apoptosis which are induced in the infected cells. Our findings indicate that A224L interacts with the proteolytic fragment of caspase-3 and inhibits the activity of this protease during ASFV infection. These observations could indicate a conserved mechanism of action for ASFV IAP and other IAP family members to suppress apoptosis.
非洲猪瘟病毒（ASFV）A224L是凋亡抑制蛋白（IAP）家族的成员。我们已经研究了病毒IAP在稳定转染细胞和ASFV感染细胞中的抗凋亡功能。当通过基因转染在Vero细胞中过表达时，A224L能够显著抑制由肿瘤坏死因子α、放线菌酮或星形孢菌素处理诱导的半胱天冬酶活性和细胞死亡。我们还观察到ASFV感染会诱导Vero细胞中的半胱天冬酶激活和凋亡。此外，使用缺乏A224L基因的ASFV缺失突变体，我们表明病毒IAP调节效应细胞死亡蛋白酶半胱天冬酶-3的蛋白水解过程以及感染细胞中诱导的凋亡。我们的研究结果表明，A224L在ASFV感染期间与半胱天冬酶-3的蛋白水解片段相互作用并抑制该蛋白酶的活性。这些观察结果可能表明ASFV IAP和其他IAP家族成员抑制凋亡的保守作用机制。
