Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge Biomedical Campus, Cambridge, United Kingdom.
J Virol. 2013 Jul;87(13):7309-13. doi: 10.1128/JVI.00647-13. Epub 2013 Apr 17.
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-α) and interleukin-6 (IL-6). These results demonstrate that TRIM21 provides a potent block to spreading infection and induces an antiviral state.
三结构域蛋白 21（TRIM21）是一种胞质免疫球蛋白受体，介导抗体依赖的细胞内中和（ADIN）。在这里，我们表明 TRIM21 能够强烈抑制复制性细胞病变病毒的传播感染，并激活先天免疫。我们使用基于定量 PCR（qPCR）的测定法来测量小鼠腺病毒 1（MAV-1）的体外复制，MAV-1 是一种在小鼠中引起剂量依赖性出血性脑炎的病毒。使用该测定法，我们表明 TRIM21 的基因缺失或 AAA ATPase p97/包含蛋白（VCP）或蛋白酶体的化学抑制导致在免疫血清存在下感染水平增加 1000 多倍。此外，抗血清中和复制的 TRIM21 介导能力是免疫小鼠体液免疫反应的一个一致特征。在免疫血清存在和感染的情况下，TRIM21 还激活促炎反应，导致肿瘤坏死因子 alpha（TNF-α）和白细胞介素 6（IL-6）的分泌。这些结果表明 TRIM21 提供了对传播感染的有效阻断，并诱导抗病毒状态。
