プレフォルディン複合体は,インターフェロン刺激による遺伝子発現を促進し,ロタウイルスVP3によって抑制されます
Yinxing Zhu1, Yanhua Song2,3, Dilip Kumar4,5
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Nature communications
|August 29, 2025
まとめ
ロタウイルスVP3タンパク質は,インターフェロン刺激遺伝子 (ISG) 発現に不可欠なプレフォルディン-UBA3複合体を阻害することによって宿主の抗ウイルス防御を妨げます. この相互作用は,ウイルス感染症に対する免疫反応を弱める.
科学分野:
- ウイルス学
- 免疫学
- 分子生物学
背景:
- インターフェロン (IFN) とインターフェロン刺激遺伝子 (ISG) は,宿主のウイルスに対する防御に不可欠です.
- ロタウイルスタンパク質VP3はインターフェロン反応を阻害することが知られているが,そのメカニズムは不明である.
研究 の 目的:
- ロタウイルスVP3が宿主の抗ウイルス免疫に敵対する分子メカニズムを解明する.
- ロタウイルスVP3と相互作用する細胞タンパク質を特定する.
主な方法:
- 高解像度質量スペクトロメトリーと組み合わせたタンデム・アフィニティ浄化により,VP3結合パートナーが特定される.
- タンパク質発現の変化を分析するためのプロテオーム全体のラベルフリー定量化.
- プレフォルディンサブユニットノックアウト細胞におけるロタウイルス感染の分析
主要な成果:
- プレフォルディン複合体は,ロタウイルスVP3の重要な細胞結合パートナーとして特定されました.
- プラフォルディンのノックアウトは ロタウイルス感染を大幅に強化しました
- プレフォルディンは,ISG発現を正に調節するUBA3 (ユビキチンのような変形活性化酵素3) の折り畳みを促進する.
- ロタウイルスVP3はプレフォルディンを直接結合し,そのシャペロン活性を抑制し,UBA3の不安定化,IRF9の低下,ISGの転写を抑制する.
結論:
- 抗ウイルス免疫に重要な新しいプレフォルディン-UBA3-IRF9-ISG軸が報告されています.
- ロタウイルスVP3は,この軸を妨害することで宿主の免疫に敵対します.
- これらの発見は,広範囲の抗ウイルス治療の開発のための潜在的なターゲットを提供します.
関連する概念動画
02:28Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
01:10Retrovirus Life Cycles
46.8K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.8K
02:30siRNA - Small Interfering RNAs
17.0K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
17.0K
01:31Regulation of the Unfolded Protein Response
2.6K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K
02:15Experimental RNAi
6.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.2K
01:29Viruses with RNA Genomes
114
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
114