Simultaneous Neutralization and Innate Immune Detection of a Replicating Virus by TRIM21

被引:35
作者
Watkinson, R. E. [1 ]
Tam, J. C. H. [1 ]
Vaysburd, M. J. [1 ]
James, L. C. [1 ]
机构
[1] MRC, Mol Biol Lab, Div Prot & Nucle Acid Chem, Cambridge CB2 2QH, England
基金
英国医学研究理事会;
关键词
MOUSE ADENOVIRUS; PROTEIN; ANTIBODIES; RECEPTOR; REPRESSION; GENE; DNA; FL;
D O I
10.1128/JVI.00647-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Tripartite motif-containing 21 (TRIM21) is a cytosolic immunoglobulin receptor that mediates antibody-dependent intracellular neutralization (ADIN). Here we show that TRIM21 potently inhibits the spreading infection of a replicating cytopathic virus and activates innate immunity. We used a quantitative PCR (qPCR)-based assay to measure in vitro replication of mouse adenovirus type 1 (MAV-1), a virus that causes dose-dependent hemorrhagic encephalitis in mice. Using this assay, we show that genetic ablation of TRIM21 or chemical inhibition of either the AAA ATPase p97/valosin-containing protein (VCP) or the proteasome results in a >1,000-fold increase in the relative level of infection in the presence of immune serum. Moreover, the TRIM21-mediated ability of antisera to block replication was a consistent feature of the humoral immune response in immunized mice. In the presence of immune sera and upon infection, TRIM21 also activates a proinflammatory response, resulting in secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). These results demonstrate that TRIM21 provides a potent block to spreading infection and induces an antiviral state.
引用
收藏
页码:7309 / 7313
页数:5
相关论文
共 21 条
[1]   The Repression Domain of the E1B 55-Kilodalton Protein Participates in Countering Interferon-Induced Inhibition of Adenovirus Replication [J].
Chahal, Jasdave S. ;
Gallagher, Courtney ;
DeHart, Caroline J. ;
Flint, S. J. .
JOURNAL OF VIROLOGY, 2013, 87 (08) :4432-4444
[2]   Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways [J].
Chou, Tsui-Fen ;
Brown, Steve J. ;
Minond, Dmitriy ;
Nordin, Brian E. ;
Li, Kelin ;
Jones, Amanda C. ;
Chase, Peter ;
Porubsky, Patrick R. ;
Stoltz, Brian M. ;
Schoenen, Frank J. ;
Patricelli, Matthew P. ;
Hodder, Peter ;
Rosen, Hugh ;
Deshaies, Raymond J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (12) :4834-4839
[3]   MOUSE ADENOVIRUS TYPE-1 CAUSES A FATAL HEMORRHAGIC ENCEPHALOMYELITIS IN ADULT C57BL/6 BUT NOT BALB/C MICE [J].
GUIDA, JD ;
FEJER, G ;
PIROFSKI, LA ;
BROSNAN, CF ;
HORWITZ, MS .
JOURNAL OF VIROLOGY, 1995, 69 (12) :7674-7681
[4]   A NEW MOUSE VIRUS APPARENTLY RELATED TO THE ADENOVIRUS GROUP [J].
HARTLEY, JW ;
ROWE, WP .
VIROLOGY, 1960, 11 (03) :645-647
[5]   AAA ATPase p97/VCP is essential for TRIM21-mediated virus neutralization [J].
Hauler, Felix ;
Mallery, Donna L. ;
McEwan, William A. ;
Bidgood, Susanna R. ;
James, Leo C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (48) :19733-19738
[6]   Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function [J].
James, Leo C. ;
Keeble, Anthony H. ;
Khan, Zahra ;
Rhodes, David A. ;
Trowsdale, John .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (15) :6200-6205
[7]  
JANASWAMI PM, 1992, J BIOL CHEM, V267, P24886
[8]   TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved [J].
Keeble, Anthony H. ;
Khan, Zahra ;
Forster, Alan ;
James, Leo C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (16) :6045-6050
[9]   HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites [J].
Kwong, PD ;
Doyle, ML ;
Casper, DJ ;
Cicala, C ;
Leavitt, SA ;
Majeed, S ;
Steenbeke, TD ;
Venturi, M ;
Chaiken, I ;
Fung, M ;
Katinger, H ;
Parren, PWLH ;
Robinson, J ;
Van Ryk, D ;
Wang, LP ;
Burton, DR ;
Freire, E ;
Wyatt, R ;
Sodroski, J ;
Hendrickson, WA ;
Arthos, J .
NATURE, 2002, 420 (6916) :678-682
[10]   MOUSE ADENOVIRUS - GROWTH OF PLAQUE-PURIFIED FL VIRUS IN CELL LINES AND CHARACTERIZATION OF VIRAL-DNA [J].
LARSEN, SH ;
NATHANS, D .
VIROLOGY, 1977, 82 (01) :182-195