MOLECULAR GENETICS OF SIMIAN IMMUNODEFICIENCY VIRUS

对人类的理解已经取得了很大的进展 获得性免疫缺陷综合征(艾滋病)。刺激性 一种逆转录病毒已被分离，其核苷酸序列 已经确定了几个分离株，并发现了新的基因 已确认身份。尽管取得了这些进展，但仍有许多工作要做 了解致病性和致病性的遗传决定因素 发病机制。在这些领域取得进展的最佳方式是 通过使用合适的动物模型来实现。猿猴 从猕猴中分离到的免疫缺陷病毒(SIV)非常 在生物学特性上与艾滋病毒相似，这两种病毒是 在抗原性上相关。SIV也会在普通恒河猴中引起艾滋病 猴子。由此可见，猕猴的SIV对于 人类艾滋病研究。 在这项建议中，不同SIV分离株的感染性克隆将被 通过分子克隆获得整合的前病毒。 它们的核苷酸序列将被确定。试管苗 病毒的生物学特性和体内致病潜能 从这些分子克隆派生出来的将被比较。混血儿 SIV将在具有不同生物学特性的病毒之间构建 性质和致病潜能，所以核苷酸 负责致病的序列和其他生物 可以识别属性。为了进一步研究分子 病毒基因的遗传学和核苷酸序列的确认 对致病性很重要，缺失和插入突变体将 构建和定点体外诱变将是 以使重要的核苷酸序列可以 被认可了。 这项研究具有重要的长期影响 开发治疗感染者的抗病毒药物，安全和 保护病毒及其致病性的有效疫苗将 极大地促进了治疗药物的开发和 有效的疫苗。

Much progress has been made toward the understanding of human acquired immune deficiency syndrome (AIDS). The causitive agent, a retrovirus, has been isolated, the nucleotide sequence of several isolates has been determined, and novel genes have been identified. In spite of these advances, much still needs to be learned regarding the genetic determinants of pathogenicity and mechanisms of pathogenesis. Progress in these areas can best be achieved through the use of suitable animal models. Simian immunodeficiency virus (SIV) isolated from macaques is very similar to HIV in its biological properties and the two viruses are related antigenically. SIV also causes AIDS in common rhesus monkeys. It thus appears that SIV of macaques is very useful for human AIDS research. In this proposal, infectious clones of different SIV isolates will be obtained through the molecular cloning of the integrated provirus. Their nucleotide sequences will be determined. The in vitro biological properties and in vivo pathogenic potential of viruses derived form these molecular clones will be compared. Hybrid SIVs will be constructed between viruses with different biological properties and pathogenic potential, so that the nucleotide sequence responsible for the pathogenicity and other biological properties can be identified. To further study the molecular genetics of the viral genes and to confirm nucleotide sequences important for pathogenicity, deletion and insertion mutants will be constructed and site-specific in vitro mutagenesis will be performed so that important nucleotide sequences can be recognized. This research has important long term consequences for development of antiviral drugs to treat the infected, and safe and effective vaccines to protect virus and its pathogenicity will greatly facilitate the development of therapeutic drugs and effective vaccines.