Shresta Sujan, Sharar Kristin L, Prigozhin Daniil M, Snider Heidi M, Beatty P Robert, Harris Eva
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720, USA.
J Immunol. 2005 Sep 15;175(6):3946-54. doi: 10.4049/jimmunol.175.6.3946.
Dengue virus (DEN), a flavivirus, causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, the most common mosquito-borne viral illnesses in humans worldwide. In this study, using STAT1(-/-) mice bearing two different mutant stat1 alleles in the 129/Sv/Ev background, we demonstrate that IFNR-dependent control of primary DEN infection involves both STAT1-dependent and STAT1-independent mechanisms. The STAT1 pathway is necessary for clearing the initial viral load, whereas the STAT1-independent pathway controls later viral burden and prevents DEN disease in mice. The STAT1-independent responses in mice with primary DEN infection included the early activation of B and NK cells as well as the up-regulation of MHC class I molecules on macrophages and dendritic cells. Infection of bone marrow-derived dendritic cell cultures with either DEN or Sindbis virus, another positive-strand RNA virus, confirmed the early vs late natures of the STAT1-dependent and STAT1-independent pathways. Collectively, these data begin to define the nature of the STAT1-dependent vs the STAT1-independent pathway in vivo.
登革病毒（DEN）是一种黄病毒，可引起登革热和登革出血热/登革休克综合征，这是全球人类中最常见的蚊媒病毒性疾病。在本研究中，我们使用在129/Sv/Ev背景下携带两种不同突变stat1等位基因的STAT1(-/-)小鼠，证明了IFNR依赖的原发性DEN感染控制涉及STAT1依赖和STAT1非依赖机制。STAT1途径对于清除初始病毒载量是必需的，而STAT1非依赖途径控制后期病毒负担并预防小鼠的DEN疾病。原发性DEN感染小鼠的STAT1非依赖反应包括B细胞和NK细胞的早期激活以及巨噬细胞和树突状细胞上MHC I类分子的上调。用DEN或另一种正链RNA病毒辛德毕斯病毒感染骨髓来源的树突状细胞培养物，证实了STAT1依赖和STAT1非依赖途径的早期与晚期性质。总体而言，这些数据开始在体内定义STAT1依赖与STAT1非依赖途径的性质。
