McCormick A Louise, Meiering Christopher D, Smith Geoffrey B, Mocarski Edward S
Department of Microbiology & Immunology, Fairchild Science Building, Stanford University School of Medicine, Stanford, CA 95304-5124, USA.
J Virol. 2005 Oct;79(19):12205-17. doi: 10.1128/JVI.79.19.12205-12217.2005.
Human cytomegalovirus carries a mitochondria-localized inhibitor of apoptosis (vMIA) that is conserved in primate cytomegaloviruses. We find that inactivating mutations within UL37x1, which encodes vMIA, do not substantially affect replication in TownevarATCC (Towne-BAC), a virus that carries a functional copy of the betaherpesvirus-conserved viral inhibitor of caspase 8 activation, the UL36 gene product. In Towne-BAC infection, vMIA reduces susceptibility of infected cells to intrinsic death induced by proteasome inhibition. vMIA is sufficient to confer resistance to proteasome inhibition when expressed independent of viral infection. Murine cytomegalovirus m38.5, whose position in the viral genome is analogous to UL37x1, exhibits mitochondrial association and functions in much the same manner as vMIA in inhibiting intrinsic cell death. This work suggests a common role for vMIA in rodent and primate cytomegaloviruses, modulating the threshold of virus-infected cells to intrinsic cell death.
人类巨细胞病毒携带一种定位于线粒体的凋亡抑制剂（vMIA），该抑制剂在灵长类巨细胞病毒中保守。我们发现，编码vMIA的UL37x1内的失活突变对TownevarATCC（Towne-BAC）中的复制没有实质性影响，Towne-BAC是一种携带β疱疹病毒保守的半胱天冬酶8激活病毒抑制剂UL36基因产物功能拷贝的病毒。在Towne-BAC感染中，vMIA降低了受感染细胞对蛋白酶体抑制诱导的内源性死亡的敏感性。当独立于病毒感染表达时，vMIA足以赋予对蛋白酶体抑制的抗性。鼠巨细胞病毒m38.5在病毒基因组中的位置与UL37x1类似，表现出线粒体关联，并且在抑制内源性细胞死亡方面的功能与vMIA非常相似。这项工作表明vMIA在啮齿动物和灵长类巨细胞病毒中具有共同作用，调节病毒感染细胞对内源性细胞死亡的阈值。
