对单个HIV-1前病毒的转录,整合和序列的并行分析
Kevin B Einkauf1, Matthew R Osborn1, Ce Gao2
1Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Cell
|January 13, 2022
概括
持续的HIV-1感染涉及转录性活跃的前病毒,而不仅仅是沉默的. 这些活跃的病毒储库在宿主选择压力下演变,挑战了抗逆转录病毒治疗 (ART) 期间病毒延迟的传统观点.
科学领域:
- 病毒学
- 基因组学
- 表观遗传学
背景情况:
- 在抗逆转录病毒治疗 (ART) 期间持续感染人类免疫缺陷病毒1型 (HIV-1) 的细胞通常被认为是转录静态的,这表明病毒潜伏.
- 然而,证据表明活跃的病毒基因表达可能发生在一些持久细胞中,这质疑了HIV-1潜伏的既定概念.
研究的目的:
- 创建一个全面的基因组和表观遗传地图的转录活跃和沉默的HIV-1前病毒.
- 在接受抑制性ART的个体中分析这些前病毒状态的纵向演变.
- 调查前病毒转录活性,宿主染色体特征和选择压力之间的关系.
主要方法:
- 开发和应用一种新的检测方法,以分析个体HIV-1前病毒的转录活性和染色体位置.
- 整合全基因组表观遗传参考数据以与染色体状态相关联.
- 在接受抑制性ART的患者中对病毒演变的纵向分析.
主要成果:
- 预病毒转录活性与融合部位附近和3D基因组接触区域的表观染色体特征的激活有关.
- 在长期的ART中,通常选择对抗转录性活跃的前病毒.
- 具有高增殖能力的大型感染细胞克隆可以克服负选择,保持活跃的前病毒.
结论:
- 这项研究揭示了转录活跃和静默的HIV-1前病毒的动态格局.
- 亲病毒转录活性受宿主表观遗传环境和选择压力的影响.
- 活跃的前病毒不是静态的,在宿主因素和细胞增殖动态的影响下演变.
相关概念视频
01:26Size and Structure of Viral Genomes
199
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...
199
02:33Retroviruses
12.8K
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’...
12.8K
00:57Viral Recombination
23.9K
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.
23.9K
01:10Retrovirus Life Cycles
47.3K
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...
47.3K
03:08LTR Retrotransposons
18.1K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
18.1K
01:29Viruses with RNA Genomes
191
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...
191