title: Mammalian Lipopolysaccharide Receptors Incorporated into the Retroviral Envelope Augment Virus Transmission.
abstract: 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.
authors.affiliation: Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wilks
authors.affiliation: 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.
authors.forename: Egil
authors.initials: E
authors.lastname: Lien
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and California Institute of Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Amy N
authors.initials: AN
authors.lastname: Jacobson
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and California Institute of Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischbach
authors.affiliation: Shock and Trauma Research Center, Medical School, University of Missouri, Kansas City, MO 64108, USA.
authors.forename: Nilofer
authors.initials: N
authors.lastname: Qureshi
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chervonsky
authors.affiliation: Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: tgolovki@bsd.uchicago.edu.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Golovkina
mesh_terms: D000818:Animals; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D007166:Immunosuppressive Agents / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008324:Mammary Tumor Virus, Mouse / Q000502:physiology*; D051379:Mice; D011485:Protein Binding; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: C556062:IL10 protein, mouse; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014759:Viral Envelope Proteins; D016753:Interleukin-10