Harcourt B H, Sanchez A, Offermann M K
Program in Genetics and Molecular Biology, Department of Internal Medicine, Emory University, Atlanta, Georgia 30322, USA.
J Virol. 1999 Apr;73(4):3491-6. doi: 10.1128/JVI.73.4.3491-3496.1999.
Ebola virus infection is highly lethal and leads to severe immunosuppression. In this study, we demonstrate that infection of human umbilical vein endothelial cells (HUVECs) with Ebola virus Zaire (EZ) suppressed basal expression of the major histocompatibility complex class I (MHC I) family of proteins and inhibited the induction of multiple genes by alpha interferon (IFN-alpha) and IFN-gamma, including those coding for MHC I proteins, 2'-5' oligoadenylate synthetase [2'-5'(A)N], and IFN regulatory factor 1 (IRF-1). Induction of interleukin-6 (IL-6) and ICAM-1 by IL-1beta was not suppressed by infection with EZ, suggesting that the inhibition of IFN signaling is specific. Gel shift analysis demonstrated that infection with EZ blocked the induction by IFNs of nuclear proteins that bind to IFN-stimulated response elements, gamma activation sequences, and IFN regulatory factor binding site (IRF-E). In contrast, infection with EZ did not block activation of the transcription factor NF-kappaB by IL-1beta. The events that lead to the blockage of IFN signaling may be critical for Ebola virus-induced immunosuppression and would play a role in the pathogenesis of Ebola virus infection.
埃博拉病毒感染具有高度致死性，并导致严重的免疫抑制。在本研究中，我们证明用扎伊尔埃博拉病毒（EZ）感染人脐静脉内皮细胞（HUVECs）会抑制主要组织相容性复合体I类（MHC I）蛋白家族的基础表达，并抑制α干扰素（IFN-α）和IFN-γ对多个基因的诱导，包括那些编码MHC I蛋白、2'-5'寡腺苷酸合成酶[2'-5'(A)N]和IFN调节因子1（IRF-1）的基因。IL-1β诱导的白细胞介素-6（IL-6）和细胞间黏附分子-1（ICAM-1）不受EZ感染的抑制，这表明对IFN信号传导的抑制具有特异性。凝胶迁移分析表明，EZ感染会阻断IFN对与IFN刺激反应元件、γ激活序列和IFN调节因子结合位点（IRF-E）结合的核蛋白的诱导。相比之下，EZ感染不会阻断IL-1β对转录因子NF-κB的激活。导致IFN信号传导受阻的事件可能对埃博拉病毒诱导的免疫抑制至关重要，并在埃博拉病毒感染的发病机制中起作用。
