GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 3746495
• 负责人: L H EVANS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746495
• 关键词: Retroviridae; Retroviridae disease; fusion gene; genetic polymorphism; genetic recombination; genetic strain; host organism interaction; immunogenetics; laboratory mouse; macrophage; microorganism classification; microorganism immunology; monoclonal antibody; murine leukemia virus; nucleic acid sequence; point mutation; provirus; virulence; virus antigen; virus genetics; virus protein; virus replication; virus virus interaction

The major focus of research in this laboratory is the genetic variation of retroviruses, including variation as a result of point mutation as well as variation due to recombination of retroviral genes. Genetic variation occurs in all retrovirus infections, including avian, murine and human retroviruses such as HIV. Most of our current studies focus on the polymorphism of recombinant host range retrovirus variants and the characterization of endogenous retroviral sequences which are involved in the generation of the variants. Inoculation of many murine retroviruses in mice results in the generation of host range variants by recombination of the inoculated virus with endogenous retroviral genes. We have identified two major antigenic subgroups of these variants distinguished by their reactivity with two monoclonal antibodies (mAbs) and have defined the position of a single amino-acid residue whose identity determines reactivity to the antibodies. Our results indicate that the two subgroups are the result of recombination of inoculated virus with two distinct families of endogenous retroviral sequences. Furthermore, we have found that inoculation of different retroviruses results in the generation of strikingly different proportions of the variant subgroups suggesting that different inoculated retroviruses preferentially recombine with different populations of endogenous retroviral genes. We are currently comparing the endogenously-derived gene sequences of variant viruses with each other and with retrovirus gene sequences found in uninfected mice. These studies should precisely identify which endogenous sequences participate in recombination to generate the host range variants. A second aspect of our studies is the mutation rate of retroviruses. In previous studies we have directly determined the mutation rate of a murine retrovirus and found that most progeny retroviruses do not sustain any point mutations during a single cycle in a fibroblastic cell line. We wish to extend these studies to determine if mutation rates are accelerated in different cell types, such as macrophages, and examine conditions which may alter mutation rates. Direct determinations of mutation rates are quite labor intensive and would limit progress in these studies. We are developing an alternative approach which exploits an antigenic conversion we have been able to effect by a single point mutation.

这个实验室的主要研究重点是遗传变异 逆转录病毒，包括点突变的结果， 以及由于逆转录病毒基因重组而引起的变异。 遗传 在所有逆转录病毒感染中，包括禽、鼠 和人类逆转录病毒如HIV。 我们目前的大部分研究都集中在 重组宿主范围逆转录病毒变异体的多态性和 内源性逆转录病毒序列的特征， 在变异体的生成中。 接种多只小鼠 小鼠中的逆转录病毒导致宿主范围变异体的产生， 接种病毒与内源性逆转录病毒基因的重组。 我们已经确定了这些变体的两个主要抗原亚组 通过与两种单克隆抗体（mAb）的反应性区分， 并确定了一个氨基酸残基的位置， 同一性决定了对抗体的反应性。 我们的研究结果表明 这两个亚群是接种的重组的结果。 具有两个不同家族的内源性逆转录病毒序列的病毒。 此外，我们发现接种不同的逆转录病毒， 结果产生了惊人的不同比例的 不同的亚组表明不同的接种逆转录病毒 优先与不同群体的内源 逆转录病毒基因。 我们目前正在比较 变异病毒的基因序列相互之间以及与逆转录病毒的基因序列 在未受感染的小鼠中发现的基因序列。 这些研究应该准确地 鉴定哪些内源序列参与重组， 生成宿主范围变量。 我们研究的第二个方面是逆转录病毒的突变率。 在 以前的研究中，我们直接确定了一个突变率， 小鼠逆转录病毒，并发现大多数子代逆转录病毒不维持 在成纤维细胞系中的单个周期期间的任何点突变。 我们希望扩展这些研究，以确定突变率是否 在不同的细胞类型中加速，如巨噬细胞，并检查 可能改变突变率的条件。 直接测定 突变率是相当劳动密集型的， 这些研究。 我们正在开发一种替代方法， 我们已经能够通过一个点来实现抗原转换， 突变