Tam Patricia E, Weber-Sanders Melissa L, Messner Ronald P
Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Virol. 2003 Nov;77(21):11849-54. doi: 10.1128/jvi.77.21.11849-11854.2003.
Mice infected with myopathic coxsackievirus B1 Tucson (CVB1(T)) develop chronic inflammatory myopathy (CIM) consisting of hind limb weakness and inflammation. Amyopathic virus variants are infectious but attenuated for CIM. In this report, viral clones, chimeras, and sequencing were used to identify viral determinants of CIM. Chimeras identified several regions involved in CIM and localized a weakness determinant to nucleotides 2493 to 3200 of VP1. Sequencing of multiple clones and viruses identified five candidate determinants that were strictly conserved in myopathic viruses with one located in the 5' untranslated region (UTR), three in the VP1 capsid, and one in the 3C protease. Taken together, these studies implicate Tyr-87 and/or Val-136 as candidate determinants of weakness. They also indicate that there are at least two determinants of inflammation and one additional determinant of weakness encoded by myopathic CVB1(T).
感染肌病性柯萨奇病毒B1图森株(CVB1(T))的小鼠会发展出慢性炎症性肌病(CIM),其特征为后肢无力和炎症。无肌病病毒变体具有传染性,但对CIM具有减毒作用。在本报告中,使用病毒克隆、嵌合体和测序来鉴定CIM的病毒决定因素。嵌合体鉴定出了几个与CIM相关的区域,并将一个弱点决定因素定位到VP1的第2493至3200个核苷酸。对多个克隆和病毒的测序确定了五个候选决定因素,这些因素在肌病性病毒中严格保守,其中一个位于5'非翻译区(UTR),三个位于VP1衣壳,一个位于3C蛋白酶。综上所述,这些研究表明Tyr-87和/或Val-136是弱点的候选决定因素。它们还表明,肌病性CVB1(T)编码至少两个炎症决定因素和一个额外的弱点决定因素。