艾滋病毒-1整合酶结合病毒RNA基因组,在病毒形态发生过程中至关重要
Jacques J Kessl1, Sebla B Kutluay2, Dana Townsend3
1Center for Retrovirus Research, Ohio State University, Columbus, OH 43210, USA; College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
Cell
|August 28, 2016
概括
艾滋病毒-1整合酶 (IN) 结合病毒RNA基因组,影响病毒组合. 这种相互作用对于产生传染性病毒颗粒至关重要,并且是全性IN抑制剂 (ALLINIs) 的目标.
科学领域:
- 病毒学
- 分子生物学
- 结构生物学
背景情况:
- 艾滋病毒-1整合酶 (IN) 对于将病毒DNA整合到宿主基因组中至关重要.
- 有证据表明,IN在病毒颗粒的成熟和形态发生中也起作用.
- 对于IN参与病毒组合的确切机制尚不清楚.
研究的目的:
- 研究HIV-1整合酶在病毒形态发生中的作用.
- 确定IN是否与成熟的病毒体内的病毒RNA基因组直接相互作用.
- 阐明全性IN抑制剂 (ALLINI) 的作用机制.
主要方法:
- 在体外结合测试以评估IN-RNA相互作用.
- 通过IN突变产生的艾滋病毒-1病毒的分析,并用ALLINI治疗.
- 电子显微镜检查病毒形态.
- 核糖核酸免疫沉以确认病毒体中的IN-RNA结合.
主要成果:
- 艾滋病毒-1整合酶 (IN) 直接与病毒RNA基因组中的特定结构元素结合.
- 破坏IN-RNA结合的突变导致异常,非传染性病毒.
- 在野生型HIV- 1中,全性IN抑制剂 (ALLINI) 破坏了IN与病毒RNA的结合,但在逃生突变中却没有.
- 这些IN替代物对核基-RNA相互作用没有影响.
结论:
- 艾滋病毒-1整合酶通过直接与病毒RNA基因组结合,在病毒粒子形态发生中起到未被描述的作用.
- 这种IN-RNA相互作用对于产生传染性病毒至关重要.
- 艾洛斯特IN抑制剂 (ALLINI) 通过在病毒组合过程中破坏这种必不可少的IN-RNA相互作用来起作用.
相关概念视频
Size and Structure of Viral Genomes
993
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
993
Viruses with RNA Genomes
1.2K
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...
1.2K
Retrovirus Life Cycles
50.3K
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...
50.3K
Retroviruses
15.6K
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’...
15.6K
Mechanisms of Retrovirus-induced Cancers
7.2K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
7.2K
siRNA - Small Interfering RNAs
18.9K
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...
18.9K


