Abrahams Melissa-Rose, Zhang Zhouning, Chien Sufan, Skerns Tim, Kotwal Girish J
Division of Medical Virology, IIDMM, University of Cape Town Medical School, Anzio Road, Observatory-7925, Cape Town, South Africa.
Ann N Y Acad Sci. 2005 Nov;1056:87-99. doi: 10.1196/annals.1352.006.
As the single-most potent virulence factor of the vaccinia virus, the 13.8-kDa protein enhances viral replication in the brain by an unknown mechanism. Due to the high energy demands of the brain and the at times inadequate energy supply and small energy reserves to support physiologic activity, the ability of this organ to support energy requirements for replication of a virus is unlikely. We investigated the possible role of the 13.8-kDa protein in the enhancement of adenosine triphosphate (ATP) utilization in the brain to sustain viral replication. In vitro and in vivo monitoring and comparison of ATP levels in mouse brain tissue infected with a wild-type vaccinia virus or a 13.8-kDa deletion strain (vGK5) revealed differences in ATP utilization and a significant difference in ATP levels in vivo after 5 days of infection. Because of poor replication of the wild-type Lister vaccinia virus in the brain, a role for the 13.8-kDa protein in the modulation of ATP levels to support viral replication in the brain could not be conclusively implicated. Evaluation of the amino acid sequence and predicted secondary structure of the 13.8-kDa protein and sequence and structural homologs thereof provided evidence of putative dimerization and adenine binding sites and a possible kinase-related function for this protein.
作为痘苗病毒最具效力的单一毒力因子，这种13.8千道尔顿的蛋白质通过未知机制增强病毒在脑中的复制。由于大脑对能量的需求很高，且有时能量供应不足、能量储备较少难以支持生理活动，该器官支持病毒复制所需能量的能力不太可能存在。我们研究了13.8千道尔顿蛋白质在增强大脑中三磷酸腺苷（ATP）利用以维持病毒复制方面可能发挥的作用。对感染野生型痘苗病毒或13.8千道尔顿缺失株（vGK5）的小鼠脑组织中的ATP水平进行体外和体内监测及比较，结果显示感染5天后ATP利用存在差异且体内ATP水平有显著差异。由于野生型李斯特痘苗病毒在脑中复制不佳，无法确凿证明13.8千道尔顿蛋白质在调节ATP水平以支持病毒在脑中复制方面的作用。对13.8千道尔顿蛋白质的氨基酸序列、预测的二级结构及其序列和结构同源物进行评估，为该蛋白质的假定二聚化和腺嘌呤结合位点以及可能的激酶相关功能提供了证据。
