Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice
Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice
复制标题
DOI：
10.4049/jimmunol.175.6.3946
复制
发表时间：
2005-09-15
影响因子：
4.4
通讯作者：
Harris, E
中科院分区：
文献类型：
--
作者：
Shresta, S;Sharar, KL;Harris, E
登革病毒（DEN）是一种黄病毒，引起登革热和登革出血热/登革休克综合征，这是全世界人类最常见的蚊媒病毒性疾病。在这项研究中，使用STAT 1（-/-）小鼠携带两个不同的突变体stat 1等位基因在129/Sv/Ev的背景下，我们证明，IFNR依赖性控制原发性DEN感染涉及STAT 1依赖和STAT 1独立的机制。STAT 1途径是清除初始病毒载量所必需的，而STAT 1非依赖性途径控制后期病毒负荷并预防小鼠中的DEN疾病。DEN感染小鼠的STAT 1非依赖性反应包括B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Sindbis病毒（另一种正链RNA病毒）感染骨髓来源的树突状细胞培养物，证实了STAT 1依赖性和STAT 1非依赖性途径的早期与晚期性质。总的来说，这些数据开始定义体内STAT 1依赖性与STAT 1非依赖性途径的性质。
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.