The product of the Herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2.
The product of the Herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2.
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DOI：
10.1186/1743-422x-5-125
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发表时间：
2008-10-22
期刊：
影响因子：
4.8
通讯作者：
Kawaguchi Y
中科院分区：
文献类型：
--
作者：
Tanaka M;Sata T;Kawaguchi Y
单纯疱疹病毒1型（HSV-1）UL 7基因在疱疹病毒科中高度保守。由于在UL 7基因中具有突变的重组HSV-1的构建尚未报道，HSV-1 UL 7参与病毒复制一直不清楚。在本研究中，我们成功地产生了UL 7无效HSV-1突变病毒MT 102，并对其进行了表征。(i)在Vero细胞中，MT 102具有复制能力，但形成的噬斑较小，产生的子代比野生型病毒少10至100倍，这取决于感染的多重性。(ii)使用质谱为基础的蛋白质组学技术，我们确定了细胞线粒体蛋白，腺嘌呤核苷酸转运蛋白2（ANT 2），作为UL 7相互作用的合作伙伴。(iii)当ANT 2在HSV-1感染的COS-7细胞中瞬时表达时，ANT 2与UL 7特异性共沉淀。(iv)用HSV-1感染的细胞进行的细胞分级分离实验在线粒体和胞质组分中检测到UL 7蛋白，而仅在线粒体组分中检测到ANT 2。这些结果表明HSV-1 UL 7参与病毒复制的重要性，并证明它与感染细胞中的ANT 2相互作用。讨论了UL 7与ANT 2相互作用的潜在生物学意义。
The herpes simplex virus 1 (HSV-1) UL7 gene is highly conserved among herpesviridae. Since the construction of recombinant HSV-1 with a mutation in the UL7 gene has not been reported, the involvement of HSV-1 UL7 in viral replication has been unclear. In this study, we succeeded in generating a UL7 null HSV-1 mutant virus, MT102, and characterized it. Our results were as follows. (i) In Vero cells, MT102 was replication-competent, but formed smaller plaques and yielded 10- to 100-fold fewer progeny than the wild-type virus, depending on the multiplicity of infection. (ii) Using mass spectrometry-based proteomics technology, we identified a cellular mitochondrial protein, adenine nucleotide translocator 2 (ANT2), as a UL7-interacting partner. (iii) When ANT2 was transiently expressed in COS-7 cells infected with HSV-1, ANT2 was specifically co-precipitated with UL7. (iv) Cell fractionation experiments with HSV-1-infected cells detected the UL7 protein in both the mitochondrial and cytosolic fractions, whereas ANT2 was detected only in the mitochondrial fraction. These results indicate the importance of HSV-1 UL7's involvement in viral replication and demonstrate that it interacts with ANT2 in infected cells. The potential biological significance of the interaction between UL7 and ANT2 is discussed.