期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 48, 页码 19733-19738出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1210659109
关键词
intracellular immunity; Cdc48
资金
- Medical Research Council [U105181010]
- European Research Council [281627-IAI]
- Kekule Mobility Fellowship from the Chemical Industry Fund of the German Chemical Industry Association
- MRC [MC_U105181010] Funding Source: UKRI
- Medical Research Council [MC_U105181010] Funding Source: researchfish
- European Research Council (ERC) [281627] Funding Source: European Research Council (ERC)
Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular virus neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity.
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