人类免疫缺陷病毒1型通过人类细胞中的DNA损伤激活
1Department of Molecular Genetics, Smith Kline and French Laboratories, King of Prussia, Pennsylvania 19406-0939.
Nature
|May 5, 1988
概括
细胞应激反应,就像紫外线的应激反应一样,显著增强人类免疫缺陷病毒1型 (HIV) 基因表达和病毒复制. 破坏DNA的药物可以重新激活潜伏的HIV感染.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 某些药物可以增强人类免疫缺陷病毒1型 (HIV) 基因表达.
- 这些药物往往会诱导细胞应激反应.
- 细胞应激反应可能在重新激活潜伏的艾滋病毒感染中发挥作用.
研究的目的:
- 研究细胞应激反应对HIV基因表达和病毒复制的影响.
- 为了确定引起压力的物质,如紫外线和线粒素C,是否可以增强HIV基因表达.
主要方法:
- 研究了紫外线和mitomycin C对人类T细胞HIV基因表达的影响.
- 评估紫外线照射后的病毒生长和发育.
- 分析了UV诱导的HIV基因表达增强背后的分子机制.
主要成果:
- 紫外线和米托米辛C增强了HIV基因表达的150倍,与tat基因产品相比.
- 紫外线诱导的增强需要转录,但不是新的蛋白质合成,与稳定的mRNA积累相关.
- 感染前的紫外线照射显著缩短了HIV病毒生长周期.
- 直接阳光也被发现可以激活HIV基因表达.
结论:
- 紫外线诱导的细胞压力有利于HIV的复制和生长.
- 损害DNA的药物和其他引起SOS类应激反应的药物可以激活HIV的表达.
- 这些发现突出了诱导压力的潜在因素,以重新激活潜伏的艾滋病毒感染和增强病毒的发展.
相关概念视频
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Size 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...


