Roberts Kimberly K, Hill Terence E, Davis Melissa N, Holbrook Michael R, Freiberg Alexander N
1Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
2Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
J Gen Virol. 2015 Jul;96(Pt 7):1651-1663. doi: 10.1099/vir.0.000119. Epub 2015 Mar 10.
Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.
裂谷热病毒（RVFV）是布尼亚病毒科白蛉病毒属中致病性最强的成员，可在人类和牲畜中引发严重疾病。直到最近，关于RVFV引发的细胞宿主反应的信息还很有限，尤其是在巨噬细胞和树突状细胞中，这些细胞在刺激针对病毒感染的适应性和先天性免疫反应中起着关键作用。为了确定宿主免疫调节细胞对感染的初始反应，用致病性RVFV毒株ZH501、减毒株MP - 12或基于MP - 12的Clone13型（rMP12 - C13型）感染原代小鼠骨髓来源的巨噬细胞（BMDM），并检测细胞因子分泌谱。感染缺乏功能性NSs毒力基因的减毒rMP12 - C13型RVFV后，T辅助（Th）1相关抗病毒细胞因子、趋化因子和各种白细胞介素的分泌迅速增加。相比之下，感染编码功能性NSs基因的减毒活疫苗MP - 12似乎会导致免疫反应延迟，而致病性ZH501几乎完全消除免疫反应。这些数据表明，NSs可以抑制BMDM抗病毒反应的成分，并支持先前的研究表明NSs可以特异性调节巨噬细胞中的I型干扰素反应。此外，我们的数据表明，ZH501和MP - 12之间的基因差异降低了MP - 12抑制抗病毒信号传导的能力，进而降低了其在BMDM中的毒力，这表明除NSs外的病毒成分在调节宿主对RVFV感染的反应中起着关键作用。
