Angulo A, Chandraratna R A, LeBlanc J F, Ghazal P
Departments of Immunology and Molecular Biology, Division of Virology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Virol. 1998 Jun;72(6):4589-600. doi: 10.1128/JVI.72.6.4589-4600.1998.
Here we report that administration of retinoids can alter the outcome of an acute murine cytomegalovirus (MCMV) infection. We show that a crucial viral control element, the major immediate-early enhancer, can be activated by retinoic acid (RA) via multiple RA-responsive elements (DR2) that bind retinoid X receptor-retinoic acid receptor (RAR) heterodimers with apparent dissociation constants ranging from 15 to 33 nM. Viral growth is dramatically increased upon RA treatment of infected tissue culture cells. Using synthetic retinoid receptor-specific agonists and antagonists, we provide evidence that RAR activation in cells is required for mediating the response of MCMV to RA. Oral administration of RA to infected immunocompetent mice selectively exacerbates an infection by MCMV, while cotreatment with an RAR antagonist protects against the adverse effects of RA on MCMV infection. In conclusion, these chemical genetic experiments provide evidence that an RAR-mediated pathway can modulate in vitro and in vivo infections by MCMV.
我们在此报告，给予维甲酸可改变急性小鼠巨细胞病毒（MCMV）感染的结果。我们表明，一个关键的病毒控制元件，即主要立即早期增强子，可被视黄酸（RA）通过多个视黄酸反应元件（DR2）激活，这些元件结合视黄醇X受体 - 视黄酸受体（RAR）异二聚体，其表观解离常数范围为15至33 nM。在用RA处理感染的组织培养细胞后，病毒生长显著增加。使用合成的视黄酸受体特异性激动剂和拮抗剂，我们提供证据表明细胞中的RAR激活是介导MCMV对RA反应所必需的。给感染的免疫活性小鼠口服RA会选择性地加重MCMV感染，而与RAR拮抗剂共同治疗可防止RA对MCMV感染的不利影响。总之，这些化学遗传学实验提供证据表明，RAR介导的途径可调节MCMV在体外和体内的感染。
