ゲノム全体のCRISPRスクリーンは,SARS-CoV-2感染にとって重要な宿主因子を明らかにします
Jin Wei1, Mia Madel Alfajaro1, Peter C DeWeirdt2
1Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Cell
|November 4, 2020
まとめ
研究者はCRISPRスクリーンを用いて,SARS-CoV-2感染の主要な宿主遺伝子を特定した. これらの発見は,HMGB1およびSWI/SNF複合体を含むコロナウイルスにとって重要な新しい治療標的と経路を明らかにしています.
科学分野:
- ウイルス学
- 遺伝学
- 免疫学
背景:
- 重症急性呼吸器症候群コロナウイルス2型 (SARS-CoV-2型) はCOVID-19を引き起こすため,治療開発のための宿主因子の特定が必要である.
- 宿主と病原体の相互作用を理解することは,ウイルス感染と病原体形成と闘うために極めて重要です.
研究 の 目的:
- ゲノム全体のCRISPRスクリーンを用いて,SARS-CoV-2感染に不可欠な宿主遺伝子を特定する.
- 新規の治療標的を発見し,新型コロナウイルス病 2019 (COVID-19) の病原性を理解する.
- SARSの系統特異性およびパンコロナウイルスの宿主因子を調査する.
主な方法:
- ゲノム全体のCRISPRスクリーンは,SARS-CoV-2,MERS-CoV,および人工ウイルスを用いたVero-E6細胞で行われました.
- HMGB1を含む特定された宿主因子の機能的検証が行われました.
- SARS-CoV-2 感染症に対する小分子抗剤の有効性を試験した.
主要な成果:
- ACE2やキャセプシンLのような既知の宿主因子が特定されました.
- HMGB1とSWI/SNF複合体を含む新規のプロウイルス遺伝子が発見されました.
- HMGB1は,ACE2発現を調節し,複数のコロナウイルスの侵入に不可欠であることが示されました.
- 特定された遺伝子を標的とした小分子阻害剤は,霊長類とヒトの細胞におけるSARS-CoV-2感染を減少させた.
結論:
- この研究は,SARS-CoV-2やその他のコロナウイルスの重要な宿主遺伝子を特定し,潜在的な治療標的を提供している.
- HMGB1とSWI/SNF複合体は,それぞれ,SARS系統特異的およびパンコロナウイルスの重要な要因を表しています.
- 特定された宿主因子を抑制することは,SARS-CoV-2に対する有効な治療戦略を示しています.
関連する概念動画
Genetic Screens
5.4K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.4K
The Antiviral System of Bacteria and Archaea: CRISPR
464
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this...
464
CRISPR/Cas9 Genome Editing
1.1K
The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
1.1K
CRISPR and crRNAs
18.3K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
18.3K
Single Nucleotide Polymorphisms-SNPs
17.5K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
17.5K


