MOLECULAR GENETICS OF SIMIAN IMMUNODEFICIENCY VIRUS

人类在理解自然界中的 获得性免疫缺陷综合症（艾滋病）。 使役 代理，逆转录病毒，已被分离，核苷酸序列的 已经确定了几个分离株，并已确定了新的基因。 鉴定 尽管取得了这些进展， 了解致病性的遗传决定因素， 发病机制。 这些领域的进展最好 通过使用合适的动物模型来实现。 猿猴 从猕猴中分离的免疫缺陷病毒（SIV）非常 与艾滋病毒的生物学特性相似， 抗原性相关。 SIV也导致普通恒河猴的艾滋病 猴子 因此，猕猴的SIV似乎非常有用， 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 通过整合的前病毒的分子克隆获得。 它们的核苷酸序列将被确定。 体外 病毒的生物学特性和体内致病潜力 将比较从这些分子克隆衍生的。 混合 SIV将在具有不同生物学特性的病毒之间构建。 性质和致病潜力，因此核苷酸 负责致病性和其他生物活性的序列 属性可以识别。 为了进一步研究 病毒基因的遗传学和确认核苷酸序列 对于致病性重要是，缺失和插入突变体将 将构建和位点特异性体外诱变， 这样重要的核苷酸序列就可以 认可. 这项研究具有重要的长期影响， 开发抗病毒药物来治疗感染者， 保护病毒及其致病性的有效疫苗将 大大促进了治疗药物的开发， 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.