TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus.
Encapsidation is a strategy almost universally employed by viruses to protect their genomes from degradation and from innate immune sensors. We show that TRIM21, which targets antibody-opsonized virions for proteasomal destruction, circumvents this protection, enabling the rapid detection and degradation of viral genomes before their replication. TRIM21 triggers an initial wave of cytokine transcription that is antibody, rather than pathogen, driven. This early response is augmented by a second transcriptional program, determined by the nature of the infecting virus. In this second response, TRIM21-induced exposure of the viral genome promotes sensing of DNA and RNA viruses by cGAS and RIG-I. This mechanism allows early detection of an infection event and drives an inflammatory response in mice within hours of viral challenge.
Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Ruth E
RE
Watkinson
Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
William A
WA
McEwan
Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Jerry C H
JC
Tam
Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Marina
M
Vaysburd
Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Leo C
LC
James
D000258:Adenovirus Infections, Human / Q000276:immunology; D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009713:Nucleotidyltransferases / Q000502:physiology*; D010587:Phagocytosis; D010850:Picornaviridae Infections / Q000276:immunology; D011971:Receptors, Immunologic; D012229:Rhinovirus; D012261:Ribonucleoproteins / Q000502:physiology*; D014777:Virus Diseases / Q000276:immunology*; D000099207:SS-A Antigen; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D007074:Immunoglobulin G; D009713:Nucleotidyltransferases; D011971:Receptors, Immunologic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase; C452820:RIGI protein, human