Wilks Jessica, Lien Egil, Jacobson Amy N, Fischbach Michael A, Qureshi Nilofer, Chervonsky Alexander V, Golovkina Tatyana V
Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA.
Division of Infectious Diseases and Immunology, Program in Innate Immunity, Department of Medicine, University of Massachusetts, Worcester, MA 01605, USA; Center of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Cell Host Microbe. 2015 Oct 14;18(4):456-62. doi: 10.1016/j.chom.2015.09.005.
The orally transmitted retrovirus mouse mammary tumor virus (MMTV) requires the intestinal microbiota for persistence. Virion-associated lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), stimulating production of the immunosuppressive cytokine IL-10 and MMTV evasion of host immunity. However, the mechanisms by which MMTV associates with LPS remain unknown. We find that the viral envelope contains the mammalian LPS-binding factors CD14, TLR4, and MD-2, which, in conjunction with LPS-binding protein (LBP), bind LPS to the virus and augment transmission. MMTV isolated from infected mice lacking these LBPs cannot engage LPS or stimulate TLR4 and have a transmission defect. Furthermore, MMTV incorporation of a weak agonist LPS from Bacteroides, a prevalent LPS source in the gut, significantly enhances the ability of this LPS to stimulate TLR4, suggesting that MMTV intensifies these immunostimulatory properties. Thus, an orally transmitted retrovirus can capture, modify, and exploit mammalian receptors for bacterial ligands to ensure successful transmission.
经口传播的逆转录病毒小鼠乳腺肿瘤病毒（MMTV）的持续存在需要肠道微生物群。病毒体相关的脂多糖（LPS）激活Toll样受体4（TLR4），刺激免疫抑制细胞因子IL-10的产生并使MMTV逃避免疫。然而，MMTV与LPS结合的机制尚不清楚。我们发现病毒包膜含有哺乳动物LPS结合因子CD14、TLR4和MD-2，它们与LPS结合蛋白（LBP）一起将LPS与病毒结合并增强传播。从缺乏这些LBP的感染小鼠中分离出的MMTV不能结合LPS或刺激TLR4，并且存在传播缺陷。此外，MMTV掺入来自肠道中普遍存在的LPS来源拟杆菌的弱激动剂LPS，显著增强了这种LPS刺激TLR4的能力，表明MMTV增强了这些免疫刺激特性。因此，一种经口传播的逆转录病毒可以捕获、修饰并利用哺乳动物的细菌配体受体来确保成功传播。
