GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 5200428
• 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/5200428
• 关键词: Retroviridae; genetic polymorphism; genetic recombination; immunogenetics; laboratory mouse; macrophage; microorganism immunology; monoclonal antibody; nucleic acid sequence; point mutation; provirus; virus antigen; virus genetics; virus protein

Genetic variation as a result of point mutation or recombination occurs in all retrovirus infections including avian, murine and human retroviruses such as HIV. Such variation often has a profound influence on the infectious, replicative and pathogenic properties of the viruses. Mice inoculated with certain retroviruses generate variant retroviruses with altered infectious properties. The variants are the result of recombination of the inoculated virus with endogenous retroviral gene sequences of the mouse. The variants utilize a different cell surface receptor for infection, thus altering the infectious host range and have been implicated in a variety of proliferative diseases in the mouse. There exist 30 to 40 distinct retroviral sequences in the mouse genome which encode the receptor binding specificity exhibited by the variants, however which of these participate in recombination is unknown. Identification of the participants in the recombination process is essential to its understanding. It is clear from previous analyses of virion RNAs that the variants are not all derived from the same endogenous sequence. Furthermore, we have identified two different antigenic subgroups of the variants which correspond to two different subgroups of endogenous sequences and have found that different retroviruses preferentially recombine with different sets of endogenous sequences. Our most recent studies have been directed at: 1) the precise identification of the endogenous sequences which participate in recombination and: 2) the identification of viral genes of the inoculated viruses which influence recombination with particular sets of endogenous sequences. Sequence comparisons of the variant viruses with retroviral gene sequences from uninfected mice have identified particular endogenous genes which give rise to the recombinant viruses. Further analyses will reveal additional endogenous genes which participate in recombination and the frequency with which they do so. With regard to the viral gene(s) which influence the specificity of recombination, we have examined variants generated after infection of mice by chimeric viruses constructed between two retroviruses which clearly differ in the subgroups of variants generated. We have found that a region of the genome which encompasses the gene encoding the nucleocapsid protein of the virus strongly influences the recombinant subgroups identified in infected mice. Further studies may more precisely determine a smaller sequence responsible for this effect and may identify other regions of the genome which influence the specificity of recombination.

由于点突变或重组而发生的遗传变异 在所有逆转录病毒感染中，包括禽类、鼠类和人类 逆转录病毒，如HIV。 这种变化往往会产生深远的影响 病毒的传染性、复制性和致病性。 接种某些逆转录病毒的小鼠产生变异的逆转录病毒 改变了传染性 这些变体是 接种病毒与内源性逆转录病毒基因的重组 小鼠的序列。 这些变体利用不同的细胞表面 感染受体，从而改变感染宿主范围， 与小鼠的多种增殖性疾病有关。 在小鼠基因组中存在30到40个不同的逆转录病毒序列 其编码变体所表现出的受体结合特异性， 然而，这些基因中哪些参与重组是未知。 识别重组过程中的参与者是 对于理解它至关重要。从以前的分析可以清楚地看出， 病毒体RNA的变体并不都来自相同的 内源序列 此外，我们还发现了两种不同的 对应于两种不同的抗原亚群的变体 亚组的内源性序列，并已发现，不同的 逆转录病毒优先与不同的内源性 序列的 我们最近的研究主要针对：1）精确的 参与的内源性序列的鉴定 重组和：2）鉴定接种的病毒基因 影响与特定内源性重组的病毒 序列的 变异病毒与逆转录病毒的序列比较 未感染小鼠的基因序列已经确定了特定的内源性 产生重组病毒的基因。 进一步分析将 揭示了参与重组的另外的内源基因， 他们这样做的频率。 关于病毒基因 影响重组的特异性，我们已经研究了 嵌合病毒感染小鼠后产生的变异体 在两种逆转录病毒之间构建， 生成的变体的子组。 我们发现， 包含编码核衣壳蛋白的基因的基因组 该病毒强烈地影响了 感染的老鼠 进一步的研究可能会更精确地确定一个较小的 序列负责这一影响，并可能确定其他地区的 影响重组特异性的基因组。