GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 2566733
• 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/2566733
• 关键词: gene induction /repression; laboratory mouse; murine leukemia virus; neoplasm /cancer genetics; protooncogene; viral carcinogenesis; viral leukemia; virus genetics

Genetic variation occurs in all retrovirus infections including avian, murine and human retroviruses such as HIV. Mice inoculated with certain retroviruses generate variant retroviruses with altered infectious properties. The variants, which utilize a different cell surface receptor for infection, result from recombination of the inoculated virus with endogenous retroviral gene sequences of the mouse. Such variants have been implicated in a variety of proliferative diseases in the mouse. One of the outcomes of variant generation is a mixed retroviral infection in which the host is infected with two or more types of viruses with differing infectious properties. Our recent studies have focussed on the interaction of murine retroviruses in mixed infections. Two modes of mixed retroviral infection have been examined. The first is a mixed infection generated by inoculation of a lymphocytic leukemia-inducing virus which readily recombines with host genes to generate host range variants. It is known that the generation of variants is necessary for this disease and it is established that the induction of leukemia is the result of the activation of host proto-oncogenes by integration of viruses in close proximity to such genes. However, since both the inoculated virus and the variants are capable of proto-oncogene activation, the requirement for host range variants is unclear. We have found that the interaction of the two virus types through pseudotyping and interference during the preleukemic phase of disease results in two distinct phases of rapid infection of the target cells. It is likely that this infectious process facilitates a highly efficient stepwise mechanism of leukemogenesis. We have also examined mixed retroviral infections generated by co-inoculation of retrovirus mixtures. We have found that co-inoculation of an erythroleukemia virus with a virus which induces a low incidence of neurological disease after a relatively long latency (3-6 months) in NFS/N mice, results in a fatal neurological disease starting 10 days after inoculation. This disease is the most rapidly fatal disease induced by any reported retrovirus with virtually all co-inoculated mice moribund or dead within two weeks after infection. We have recently established that the gene encoding the erythroleukemia viral envelope glycoprotein is responsible for this effect. Further studies are directed at quantification of viral pseudotyping in co-inoculated mice and the effect of co-inoculation on the infection and distribution of both virus types in the central nervous system.

遗传变异发生在所有逆转录病毒感染中， 鼠和人逆转录病毒如HIV。 小鼠接种了某些 逆转录病毒产生变异的逆转录病毒， 特性. 这些变体利用不同的细胞表面， 感染受体，由接种病毒重组而成 小鼠的内源性逆转录病毒基因序列。 此类变体 与小鼠的多种增殖性疾病有关。 变异产生的结果之一是混合逆转录病毒 宿主感染两种或两种以上的 具有不同感染特性的病毒。 我们最近的研究 集中在混合感染中鼠逆转录病毒的相互作用。 混合逆转录病毒感染的两种模式已被审查。 第一 是一种混合感染，通过接种淋巴细胞 容易与宿主基因重组， 生成主机范围变量。 据了解， 变异是这种疾病所必需的，并且已经确定， 白血病的诱导是宿主细胞活化的结果， 原癌基因的整合病毒在接近这样的 基因. 然而，由于接种的病毒和变异体都是 能够激活原癌基因，要求宿主范围 变体不清楚。 我们发现两种病毒的相互作用 在白血病前期通过假分型和干扰分型 疾病的快速感染导致两个不同的阶段， 靶细胞 很可能这种传染过程促进了 白血病发生的高效阶梯机制。 我们还 检查了混合逆转录病毒感染产生的共同接种 逆转录病毒混合物。 我们发现， 红白血病病毒与引起低发病率的 在相对长的潜伏期（3-6个月）后， NFS/N小鼠，导致10天开始的致命神经系统疾病 接种后。 这种疾病是最迅速致命的疾病 几乎所有共接种小鼠均由任何已报告的逆转录病毒诱导 感染后两周内濒死或死亡。 我们最近 确定编码红白血病病毒包膜的基因 糖蛋白负责这种作用。 进一步的研究 针对共接种小鼠中病毒假型的定量 同时研究了共接种对黑胫病侵染和分布的影响 这两种病毒都存在于中枢神经系统