title: Intracellular antibody receptor TRIM21 prevents fatal viral infection.
abstract: Host species have evolved mechanisms that can inhibit pathogen replication even after a cell has been successfully invaded. Here we show that tripartite-motif protein 21 (TRIM21), a ubiquitously expressed E3 ubiquitin ligase that targets viruses inside the cytosol, protects mice against fatal viral infection. Upon infection with mouse adenovirus-1, naive mice lacking TRIM21 succumb to encephalomyelitis within 7 d. In contrast, wild-type mice rapidly up-regulate TRIM21 and control viremia. Trim21 heterozygous mice have a haploinsufficiency phenotype in which reduced TRIM21 expression leads to a viral load that is higher than wild types but lower than knockouts. TRIM21 is a high-affinity antibody receptor that allows antibodies to operate inside an infected cell. In passive transfer experiments at high viral dose, antisera that fully protects wild-type mice fails to protect most Trim21 knockout animals. These results demonstrate that TRIM21 provides potent antiviral protection and forms an important part of the humoral immune response.
authors.affiliation: Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
authors.forename: Marina
authors.initials: M
authors.lastname: Vaysburd
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Watkinson
authors.forename: Helen
authors.initials: H
authors.lastname: Cooper
authors.forename: Martin
authors.initials: M
authors.lastname: Reed
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Connell
authors.forename: Jackie
authors.initials: J
authors.lastname: Smith
authors.forename: James
authors.initials: J
authors.lastname: Cruickshanks
authors.forename: Leo C
authors.initials: LC
authors.lastname: James
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000502:physiology*; D014777:Virus Diseases / Q000401:mortality / Q000517:prevention & control*; D000099207:SS-A Antigen
chemical_list: D012261:Ribonucleoproteins; D000099207:SS-A Antigen