Sarkar Tapati, Das Sukhen, Nandy Papiya, Bhowmick Rahul, Nandy Ashesh
Department of Physics, Jadavpur University, Kolkata 700 032, India.
Department of Physics, Jadavpur University, Kolkata 700 032, India.
Comput Biol Chem. 2014 Aug;51:51-6. doi: 10.1016/j.compbiolchem.2014.05.003. Epub 2014 Jun 4.
Rotavirus, the major cause of infantile nonbacterial diarrhea, was found to be associated with development of diabetes-associated auto-antibodies. In our study we tried to find out further potential autoimmune threats of this virus using bioinformatics approach. We took rotaviral proteins to study similarity with Homo sapiens proteome and found most conserved structural protein VP6 matches at two regions with ryanodine receptor, an autoimmune target associated with myasthenia gravis. Myasthenia gravis, a chronic neurodegenerative autoimmune disorder with no typical known reason, is characterized by fluctuating muscle weakness which is typically enhanced during muscular effort. Affected patients generate auto antibodies against mainly acetyl choline receptor and sarcoplasmic reticulum calcium-release channel protein ryanodine receptor. Further, we observed that two regions which matched with ryanodine receptor remain conserved in all circulating rotaviral strains and showed significant antigenecity with respect to myasthenia gravis associated HLA haplotypes. Overall, our study detected rotaviral VP6 as a potential threat for myasthenia gravis and enlighten an area of virus associated autoimmune research.
轮状病毒是婴儿非细菌性腹泻的主要病因,被发现与糖尿病相关自身抗体的产生有关。在我们的研究中,我们试图使用生物信息学方法进一步探究这种病毒潜在的自身免疫威胁。我们提取轮状病毒蛋白,研究其与人类蛋白质组的相似性,发现最保守的结构蛋白VP6在两个区域与兰尼碱受体匹配,兰尼碱受体是一种与重症肌无力相关的自身免疫靶点。重症肌无力是一种原因不明的慢性神经退行性自身免疫疾病,其特征是肌肉无力波动,在肌肉活动时通常会加重。受影响的患者主要产生针对乙酰胆碱受体和肌浆网钙释放通道蛋白兰尼碱受体的自身抗体。此外,我们观察到与兰尼碱受体匹配的两个区域在所有流行的轮状病毒株中都保持保守,并且相对于与重症肌无力相关的HLA单倍型显示出显著的抗原性。总体而言,我们的研究检测到轮状病毒VP6是重症肌无力的潜在威胁,并为病毒相关自身免疫研究开辟了一个领域。