レトロウイルスDNA統合:統合中間体の構造
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Cell
|August 12, 1988
まとめ
モローニー・マウリン白血病ウイルス (Mo-MLV) のDNAは,最初に循環する必要なく,直接宿主DNAに統合されます. この研究は,バクテリアファージのMu転移に類似した,レトロウイルスDNA統合中の重要な中間構造を明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- ウイルス学 ウイルス学 ウイルス学
- 遺伝学 遺伝学とは
背景:
- レトロウイルスDNA統合は,ウイルスのライフサイクルにおける重要なステップです.
- 統合の正確なメカニズムを理解することは,抗ウイルス治療の開発に不可欠です.
- 以前のモデルでは,統合の前提条件としてDNA循環化が提案されていた.
研究 の 目的:
- モローニーマウリン白血病ウイルス (Mo-MLV) 統合中のDNA中間体の構造を解明する.
- Mo-MLV統合機構を既知の転置経路と比較する.
- 線形ウイルスDNAが直接統合できるかどうかを判断する.
主な方法:
- 外因的に添加された標的DNAを用いた細胞フリー統合反応.
- Mo-MLVコア粒子によって生成されるウイルスのDNA中間物質の分析.
- 統合インターミディアムの構造的特徴.
主要な成果:
- Mo-MLV統合における推定DNA中間体が特定されました.
- 中間構造は,3' LTR端が標的DNAに結合し,5' ウイルスのDNA端が結合していないことを示した.
- 中間の5'LTRの末端は,統合されていない線形ウイルスDNAの末端と一致した.
結論:
- Mo-MLV DNA統合は,循環化を回避して,線形から直接発生することができます.
- 統合メカニズムは,バクテリアファージのMu転移と類似性を共有しています.
- この発見は,レトロウイルスDNA統合の分子詳細に関する重要な洞察を提供します.
関連する概念動画
01:10Retrovirus Life Cycles
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 retrovirus to...
00:57Viral Recombination
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.
02:33Retroviruses
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’...
03:08LTR Retrotransposons
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...
01:51Mechanisms of Retrovirus-induced Cancers
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...
01:26Size and Structure of Viral Genomes
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...