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

Vaysburd M,Watkinson RE,Cooper H,Reed M,O'Connell K,Smith J,Cruickshanks J,James LC

doi

10.1073/pnas.1301918110

subject

Has Abstract

pub_date

2013-07-23 00:00:00

pages

12397-401

issue

30

eissn

0027-8424

issn

1091-6490

pii

1301918110

journal_volume

110

pub_type

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