流感A病毒通过隔离双链RNA来规避天生的免疫反应
Masahiro Nakano1,2,3, Sho Miyamoto1,4, Chiho Ohnishi1
1Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Journal of virology
|September 8, 2025
概括
流感A病毒 (IAV) 通过隔离双链RNA (dsRNA) 来逃避天生的免疫力. 病毒非结构蛋白1 (NS1) 掩盖dSRNA,防止免疫激活. 删除NS1允许dsRNA转位和免疫反应.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 双链RNA (dsRNA) 是对抗病毒感染的先天免疫力的强有力的触发器.
- 据认为,A型流感病毒 (IAV) 很少在感染细胞内产生可检测的dsRNA.
- 病毒核糖蛋白 (vRNP) 复合体在体外IAVRNA合成过程中产生循环dRNA.
研究的目的:
- 研究IAV在受感染细胞内隔离dsrna的机制.
- 确定病毒非结构蛋白1 (NS1) 在dSRNA连接中的作用.
- 为了阐明IAV如何规避尽管dRNA的生产天生的免疫反应.
主要方法:
- 在IAV感染的细胞中检测dSRNA,包括缺乏NS1和核出口蛋白 (NEP) 表达的细胞.
- 从受感染细胞中分离循环dRNA-vRNP复合体.
- 高速原子力显微镜可视化dRNA的NS1掩盖.
- 对dSRNA和干扰素调节因子3 (IRF3) 转位在野生类型和突变IAV感染细胞的分析.
主要成果:
- 在缺乏NS1和NEP的IAV感染细胞中检测到dsRNAs.
- 发现NS1分子掩盖了由vRNP产生的整个循环dRNA.
- 在野生型IAV感染中,dsRNA被隔离在核中,但在NS1删除突变病毒感染中被转移到细胞质中.
- dsRNA的细胞质转位触发了IRF3的核转位,表明免疫反应被激活了.
结论:
- IAV采用了dsrna封存的策略,以逃避天生的免疫力.
- NS1在掩盖病毒dsRNA方面发挥着至关重要的作用,防止其被细胞质传感器识别.
- 与vRNP相关的dsRNA转移到细胞质,可以在NS1缺席时触发先天性免疫反应.
相关概念视频
01:29Viruses with RNA Genomes
840
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...
840
02:28Leaky Scanning
5.6K
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...
5.6K
01:29Immune Response Against Viral Pathogens
1.8K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.8K
02:30siRNA - Small Interfering RNAs
18.4K
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...
18.4K
02:15Experimental RNAi
7.3K
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...
7.3K
00:57Viral Recombination
24.9K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
24.9K