title: Critical role for bone marrow stromal antigen 2 in acute Chikungunya virus infection.
abstract: Bone marrow stromal antigen 2 (BST-2; also known as tetherin or CD317) is an IFN-inducible gene that functions to block the release of a range of nascent enveloped virions from infected host cells. However, the role of BST-2 in viral pathogenesis remains poorly understood. BST-2 plays a multifaceted role in innate immunity, as it hinders retroviral infection and possibly promotes infection with some rhabdo- and orthomyxoviruses. This paradoxical role has probably hindered exploration of BST-2 antiviral function in vivo. We reported previously that BST-2 tethers Chikungunya virus (CHIKV)-like particles on the cell plasma membrane. To explore the role of BST-2 in CHIKV replication and host protection, we utilized CHIKV strain 181/25 to examine early events during CHIKV infection in a BST-2(-/-) mouse model. We observed an interesting dichotomy between WT and BST-2(-/-) mice. BST-2 deficiency increased inoculation site viral load, culminating in higher systemic viraemia and increased lymphoid tissues tropism. A suppressed inflammatory innate response demonstrated by impaired expression of IFN-α, IFN-γ and CD40 ligand was observed in BST-2(-/-) mice compared with the WT controls. These findings suggested that, in part, BST-2 protects lymphoid tissues from CHIKV infection and regulates CHIKV-induced inflammatory response by the host.
authors: Interdisciplinary Graduate Program in Molecular and Cellular Biology (MCB), University of Iowa, Iowa City, IA, USA.|Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors: Wadie D
authors: WD
authors: Mahauad-Fernandez
authors: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors: Philip H
authors: PH
authors: Jones
authors: Interdisciplinary Graduate Program in Molecular and Cellular Biology (MCB), University of Iowa, Iowa City, IA, USA.|Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors: Chioma M
authors: CM
authors: Okeoma
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018925:Chemokines / Q000235:genetics; D065632:Chikungunya Fever / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D002646:Chikungunya virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D008562:Membrane Glycoproteins; C513868:BST2 protein, mouse; D000074010:Bone Marrow Stromal Antigen 2