Henke A, Nestler M, Strunze S, Saluz H P, Hortschansky P, Menzel B, Martin U, Zell R, Stelzner A, Munder T
Institute of Virology, Medical Center, Friedrich Schiller University Jena, Winzerlaer Strasse 10, D-07745 Jena, Germany.
Virology. 2001 Oct 10;289(1):15-22. doi: 10.1006/viro.2001.1082.
Infections with coxsackievirus B3 (CVB3) are common causes of myocarditis in humans. One detail of CVB3-induced pathogenesis is apoptosis. The interaction between the capsid protein VP2 of the myocardial virus variant CVB3H3 and the proapoptotic host cell protein Siva has recently been observed. In order to characterize the interaction between both proteins more precisely, the binding activity of the CVB3H3 VP2 to Siva was compared to that of the mutant virus CVB3H310A1 VP2. We found that the asparagine at position 165 in VP2 is essential for a stable interaction with Siva influencing also the induction of apoptosis, viral spread, and inflammatory responses in vivo. Furthermore, the specific binding site of Siva to VP2 is located at amino acid positions 118-136. Together, these results show that the interaction between VP2 of CVB3H3 and Siva is a highly specific process involving distinct amino acids on both proteins that most likely influence the outcome of CVB3-caused disease.
柯萨奇病毒B3（CVB3）感染是人类心肌炎的常见病因。CVB3诱导发病机制的一个细节是细胞凋亡。最近观察到心肌病毒变异株CVB3H3的衣壳蛋白VP2与促凋亡宿主细胞蛋白Siva之间的相互作用。为了更精确地表征这两种蛋白之间的相互作用，将CVB3H3 VP2与Siva的结合活性与突变病毒CVB3H310A1 VP2进行了比较。我们发现VP2中第165位的天冬酰胺对于与Siva的稳定相互作用至关重要，这也影响体内细胞凋亡的诱导、病毒传播和炎症反应。此外，Siva与VP2的特异性结合位点位于氨基酸位置118 - 136。总之，这些结果表明CVB3H3的VP2与Siva之间的相互作用是一个高度特异性的过程，涉及两种蛋白上不同的氨基酸，这很可能影响CVB3所致疾病的结果。
