Resistance to Rabies Virus Infection Conferred by the PMLIV Isoform
Resistance to Rabies Virus Infection Conferred by the PMLIV Isoform
复制标题
DOI：
10.1128/jvi.01286-10
复制
发表时间：
2010-10-01
影响因子：
5.4
通讯作者：
Chelbi-Alix, Mounira K.
中科院分区：
文献类型：
--
作者：
Blondel, Danielle;Kheddache, Sabrina;Chelbi-Alix, Mounira K.
各种报道表明，PML和PML核体(NBS)参与了针对不同细胞质复制的RNA病毒的内在抗病毒反应。PML与小泛素样修饰物(SUMO)的结合是其在NBS中定位所必需的。PML在体内显示出抗病毒作用，因为PML缺陷使小鼠更容易感染横纹病毒水泡性口炎病毒(VSV)。来自这些小鼠的细胞对狂犬病病毒的感染也更敏感，狂犬病病毒是弹状病毒家族的另一个成员。单个基因的选择性剪接导致合成几种PML亚型，这些亚型被归类为七个组，命名为PMLI至-VII。我们在此报道，缺失外显子5的PMLIV或PMLIVa的表达抑制了病毒的mRNA和蛋白质合成，导致病毒复制减少。然而，其他核异构体(PMLI至-VI)和细胞质PMLVIIb的表达未能削弱病毒的产生。这种抗病毒作用需要PMLIV SUMO化，因为PMLIV 3KR没有观察到这种作用，在PMLIV 3KR中，参与相扑结合的赖氨酸发生了突变。因此，PMLIV和PMLIVa可能通过它们共同的C-末端区域与特定的Nb蛋白伙伴相互作用而发挥这种异构体特异性的功能。
Various reports implicate PML and PML nuclear bodies (NBs) in an intrinsic antiviral response targeting diverse cytoplasmic replicating RNA viruses. PML conjugation to the small ubiquitin-like modifier (SUMO) is required for its localization within NBs. PML displays antiviral effects in vivo, as PML deficiency renders mice more susceptible to infection with the rhabdovirus vesicular stomatitis virus (VSV). Cells derived from these mice are also more sensitive to infection with rabies virus, another member of the rhabdovirus family. Alternative splicing from a single gene results in the synthesis of several PML isoforms, and these are classified into seven groups, designated PMLI to -VII. We report here that expression of PMLIV or PMLIVa, which is missing exon 5, inhibited viral mRNA and protein synthesis, leading to a reduction in viral replication. However, the expression of other nuclear isoforms (PMLI to -VI) and cytoplasmic PMLVIIb failed to impair viral production. This antiviral effect required PMLIV SUMOylation, as it was not observed with PMLIV 3KR, in which the lysines involved in SUMO conjugation were mutated. Thus, PMLIV and PMLIVa may exert this isoform-specific function through interaction with specific NB protein partners via their common C-terminal region.