第二位点逆转HIV-1包膜蛋白基板突变映射到矩阵蛋白质的基板突变
Ayna Alfadhli1, CeAnn Romanaggi1, Robin Lid Barklis1
1Department of Molecular Microbiology and Immunology, Oregon Health & Sciences University, Portland, Oregon, USA.
Journal of virology
|January 9, 2024
概括
一种新的矩阵 (MA) 蛋白质突变通过增强包裹 (Env) 纳入病毒来拯救HIV-1复制. 这一发现澄清了Env蛋白如何组装成病毒颗粒,这对于理解HIV-1组装和潜在的治疗点至关重要.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 艾滋病毒-1包裹 (Env) 蛋白质的细胞质尾巴 (CT) 形成了基板结构,对病毒组装至关重要.
- 对HIV-1复制来说,Env被纳入病毒体是必不可少的,特别是在限制性T细胞系中.
- 病毒矩阵 (MA) 蛋白在Env的结合和病毒颗粒的形成中起作用.
研究的目的:
- 为了识别和描述HIV-1 Env基板突变的第二位抑制剂.
- 阐明一种新型MA突变拯救病毒复制缺陷的机制.
- 了解MA蛋白和Env CT在病毒组装中的相互作用.
主要方法:
- 局部定向的突变发生引入HIV-1MA和Env蛋白中的突变.
- 在限制性和允许性T细胞系中进行病毒复制测试.
- 单轮感染测定用于测量病毒传染性.
- 对Env纳入病毒体的分析.
主要成果:
- 在MA蛋白 (MA-34) 中的残留34位突变挽救了受限细胞中因Env基板突变而受损的复制.
- MA-34使Env在病毒中被纳入的数量增加了3倍,病毒的感染能力增加了10倍.
- MA-34的抑制活动取决于Env CT,不影响Env走私或融合.
结论:
- MA残留34在稳定Env纳入HIV-1病毒中起着至关重要的作用.
- 这些发现表明,MA-34诱导了形状变化,稳定了MA格子中的trimer-trimer相互作用和/或MA-CT关联.
- 这项研究为HIV-1 Env组装和病毒颗粒形成的机制提供了新的见解.
关键词:
艾滋病病毒-1 艾滋病病毒-1更多相关视频
10:50Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
9.6K
09:31Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
17.7K
相关概念视频
00:36Viral Mutations
32.3K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.3K
02:28Leaky Scanning
5.1K
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...
5.1K
02:33Retroviruses
12.3K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.3K