Sheeppox Virus SPPV14 Encodes a Bcl-2-Like Cell Death Inhibitor That Counters a Distinct Set of Mammalian Proapoptotic Proteins
Sheeppox Virus SPPV14 Encodes a Bcl-2-Like Cell Death Inhibitor That Counters a Distinct Set of Mammalian Proapoptotic Proteins
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DOI：
10.1128/jvi.01115-12
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发表时间：
2012-08
影响因子：
5.4
通讯作者：
T. Okamoto;Stephanie A. Campbell;Ninad Mehta;J. Thibault;P. Colman;M. Barry;D. Huang;M. Kvansakul
中科院分区：
文献类型：
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作者：
T. Okamoto;Stephanie A. Campbell;Ninad Mehta;J. Thibault;P. Colman;M. Barry;D. Huang;M. Kvansakul
许多病毒表达程序性细胞死亡（细胞凋亡）的抑制剂，从而对抗宿主的防御，否则会迅速清除感染的细胞。为了解决这个问题，病毒如腺病毒和疱疹病毒表达哺乳动物促生存蛋白Bcl-2的可识别同源物。相反，大多数痘病毒缺乏病毒Bcl-2（vBcl-2）同源物，这些同源物很容易通过序列相似性来识别。一种这样的病毒，粘液瘤病毒，这是粘液瘤病的病原体，表达一种毒力因子，是一种有效的细胞凋亡抑制剂。尽管与Bcl-2的序列相似性很少，粘液瘤病毒M11 L采用几乎相同的三维折叠。我们使用M11 L作为诱饵，在序列相似性搜索其他Bcl-2样蛋白，并确定了6个推定的vBcl-2蛋白痘病毒。一些是有效的细胞凋亡抑制剂，特别是羊痘病毒SPPV 14，它抑制由多种药物诱导的细胞死亡。重要的是，SPPV 14补偿了牛痘病毒中抗凋亡F1 L的损失，并直接对抗细胞死亡介质Bax和巴克。SPPV 14还参与了一个独特的促进死亡的BH 3配体亚组，包括Bim，Puma，Bmf和Hrk。这表明SPPV 14可能被选择作为羊痘病毒的毒力因子的特定生物学作用。
ABSTRACT Many viruses express inhibitors of programmed cell death (apoptosis), thereby countering host defenses that would otherwise rapidly clear infected cells. To counter this, viruses such as adenoviruses and herpesviruses express recognizable homologs of the mammalian prosurvival protein Bcl-2. In contrast, the majority of poxviruses lack viral Bcl-2 (vBcl-2) homologs that are readily identified by sequence similarities. One such virus, myxoma virus, which is the causative agent of myxomatosis, expresses a virulence factor that is a potent inhibitor of apoptosis. In spite of the scant sequence similarity to Bcl-2, myxoma virus M11L adopts an almost identical 3-dimensional fold. We used M11L as bait in a sequence similarity search for other Bcl-2-like proteins and identified six putative vBcl-2 proteins from poxviruses. Some are potent inhibitors of apoptosis, in particular sheeppox virus SPPV14, which inhibited cell death induced by multiple agents. Importantly, SPPV14 compensated for the loss of antiapoptotic F1L in vaccinia virus and acts to directly counter the cell death mediators Bax and Bak. SPPV14 also engages a unique subset of the death-promoting BH3-only ligands, including Bim, Puma, Bmf, and Hrk. This suggests that SPPV14 may have been selected for specific biological roles as a virulence factor for sheeppox virus.