title: TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice.
abstract: West Nile virus (WNV) is a neurotropic ssRNA flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human TLR7 and TLR8 and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. In this article, we report that TLR8-deficient (Tlr8-/-) mice were resistant to WNV infection compared with wild-type controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8-/-mice were attributed to overexpression of Tlr7 and IFN-stimulated gene-56 expression, whereas reduced expression of the proapoptotic gene coding Bcl2-associated X protein was observed. Interestingly, suppressor of cytokine signaling (SOCS)-1 directly associated with TLR8, but not with TLR7, indicating a novel role for TLR8 regulation of SOCS-1 function, whereas selective small interfering RNA knockdown of Socs-1 resulted in induced IFN-stimulated gene-56 and Tlr7 expression following WNV infection. Collectively, we report that TLR8 coupling with SOCS-1 inhibits TLR7-mediated antiviral immunity during WNV infection in mice.
authors: Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406.
authors: Amber M
authors: 0000-0002-1657-3618
authors: AM
authors: Paul
authors: Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406.
authors: Dhiraj
authors: D
authors: Acharya
authors: Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406.
authors: Linda
authors: 0000-0003-3077-8748
authors: L
authors: Le
authors: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520.|Department of Microbiology and Immunology, School of Medicine, New York Medical College, Valhalla, NY 10595.
authors: Penghua
authors: P
authors: Wang
authors: Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center, Jackson, MS 39216.
authors: Dobrivoje S
authors: 0000-0002-1891-5730
authors: DS
authors: Stokic
authors: Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center, Jackson, MS 39216.
authors: A Arturo
authors: AA
authors: Leis
authors: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France.
authors: Lena
authors: 0000-0003-4619-697X
authors: L
authors: Alexopoulou
authors: Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033.
authors: Terrence
authors: T
authors: Town
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; and.|Howard Hughes Medical Institute, New Haven, CT 06520.
authors: Richard A
authors: 0000-0003-4461-0778
authors: RA
authors: Flavell
authors: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520.|Howard Hughes Medical Institute, New Haven, CT 06520.
authors: Erol
authors: E
authors: Fikrig
authors: Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406; fengwei.bai@usm.edu.
authors: Fengwei
authors: F
authors: Bai
mesh_terms: D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000276:immunology*; D014901:West Nile Fever / Q000235:genetics / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*
chemical_list: C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8