Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1 beta-converting enzyme and protects virus-infected cells from TNF- and Fas-mediated apoptosis, but does not prevent IL-1 beta-induced fever
Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1 beta-converting enzyme and protects virus-infected cells from TNF- and Fas-mediated apoptosis, but does not prevent IL-1 beta-induced fever
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DOI：
10.1099/0022-1317-78-3-677
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发表时间：
1997-03-01
影响因子：
3.8
通讯作者：
Smith, GL
中科院分区：
文献类型：
--
作者：
Kettle, S;Alcami, A;Smith, GL
牛痘病毒（VV）毒株Western Reserve B13 R基因编码一种38.5 kDa的细胞内多肽，该多肽对于体外病毒复制是非必需的，并且在鼠鼻内模型中不影响病毒毒力。该蛋白质与牛痘病毒细胞因子应答调节剂A（crmA）蛋白具有92%的氨基酸同一性，该蛋白质抑制白细胞介素（IL）-1 β转化酶（ICE）。在这里，我们表明，从THP-1细胞感染的VV株表达B13 R的提取物阻止裂解的体外转录和翻译成成熟的IL-1 β的前IL-1 β。类似地，用表达B13 R的VV感染的THP-1细胞在原位低效地将pro-IL-1 β加工成成熟IL-1 β。尽管B13 R抑制ICE，但它不能预防感染小鼠的发热，这是由IL-1 β介导的全身效应。相反，发热是由基因B15 R编码的VV IL-1 β受体控制的，与单独缺失B15 R相比，缺失B13 R和B15 R基因两者并不增加发热反应。然而，B13 R蛋白确实阻断由抗pas抗体或肿瘤坏死因子（TNF）和放线菌酮介导的细胞凋亡。铬释放和显微镜分析显示，用野生型VV株WR或B13 R基因已重新插入B13 R缺失突变体的回复突变体病毒感染的细胞比未感染的细胞或缺失突变体感染的细胞对抗Fas和TNF介导的细胞凋亡更有抗性。
The vaccinia virus (VV) strain Western Reserve B13R gene encodes a 38.5 kDa intracellular polypeptide that is non-essential for virus replication in vitro and does not affect virus virulence in a murine intranasal model. The protein has 92% amino acid identity with the cowpox virus cytokine response modifier A (crmA) protein which inhibits the interleukin (IL)-1 beta converting enzyme (ICE). Here, we show that extracts from THP-1 cells infected with VV strains expressing B13R prevent the cleavage of in vitro transcribed and translated pro-IL-1 beta into mature IL-1 beta. Similarly, THP-1 cells infected with VVs expressing B13R process pro-IL-1 beta into mature IL-1 beta inefficiently in situ, Despite its inhibition of ICE, B13R does not prevent fever in infected mice, a systemic effect mediated by IL-1 beta. Instead, fever is controlled by the VV IL-1 beta receptor, encoded by gene B15R, and deletion of both the B13R and B15R genes did not increase the febrile response compared to deletion of B15R alone, The B13R protein does, however, block apoptosis mediated by anti-pas antibodies or by tumour necrosis factor (TNF) and cycloheximide, Using DNA fragmentation, chromium release and microscopic analyses it was shown that cells infected with wild-type VV strain WR, or a revertant virus in which the B13R gene had been re-inserted into the B13R deletion mutant, are more resistant than uninfected cells or deletion mutant-infected cells to apoptosis mediated by anti-Fas and TNF.