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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.

SUBMITTER: Vaysburd M 

PROVIDER: S-EPMC3725055 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Intracellular antibody receptor TRIM21 prevents fatal viral infection.

Vaysburd Marina M   Watkinson Ruth E RE   Cooper Helen H   Reed Martin M   O'Connell Kevin K   Smith Jackie J   Cruickshanks James J   James Leo C LC  

Proceedings of the National Academy of Sciences of the United States of America 20130709 30


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  ...[more]

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