DIVERSITY AND PATHOGENESIS OF SIVAGM

在它们的原生栖息地，30-50%的非洲绿色猴 对猴免疫缺陷病毒（SIV）有反应的抗体。 然而，加勒比海绿色猴子是SIV阴性。 尽管一些 被囚禁的猕猴被发现患有SIV和艾滋病， 迄今为止，它们在亚洲的原生栖息地也是SIV 阴性 人和非人灵长类动物慢病毒都是已知的 在HIV-2和SIVmac之间存在遗传差异， 分离物，我们的分析表明， SIVagm是惊人的广泛。 因此，拟议的研究 两大目标。 一是继续寻找SIVagm分离株 与HIV-1、HIV-2或SIVmac密切相关。 另一个是 为了确定病毒和/或宿主因素是否在 这些病毒的致病性和种属特异性。 将从非洲绿色中获得其他SIVagm分离株 分布在非洲各地的猴子。 病毒 将通过gag-pol基因特异性探针筛选分离物。 的 与HIV-1、HIV-2或SIVagm分离株密切相关的病毒可能导致 我们来确定导致艾滋病的慢病毒的起源， 人类 SIVagm和SIVagm的致病潜力和种属特异性 将在同源和异源猴中检查SIVmac 物种 这些分析将指导我们寻找病毒， /或对发病重要的宿主因素。 如果病毒因素 证明是重要的尝试将作出定位致病 通过产生杂交病毒;替换基因或 非致病性菌株与致病性菌株的区域 一个如果所有试图确定病毒因素对 那么我们可能不得不得出结论， 因素是重要的。 然后将尝试识别 靶细胞的差异，定义宿主反应和其他 宿主的遗传因素。

In their native habitat, 30-50% of African green monkeys have antibodies reactive to simian immunodeficiency virus (SIV). However, Caribbean green monkeys are SIV negative. Although some macaques in captivity are found with SIV and AIDS, macaques in their native habitat of asia examined to date have also been SIV negative. Both human and non-human primate lentiviruses are know to be genetically divergent among individual HIV-2, and SIVmac isolates, our analysis indicate that the genetic diversity of SIVagm is amazingly extensive. Therefore the proposed studies have two major goals. One is to continue search for SIVagm isolates that are closely related to HIV-1, HIV-2, or SIVmac. The other is to determine whether viral and /or host factors are important in pathogenesis and species specificity of these viruses. Additional SIVagm isolates will be obtained form African green monkeys from geographically dispersed regions of Africa. The viral isolates will be screened by gag-pol gene-specific probes. The ones closely related to HIV-1, HIV-2, or SIVagm isolates may lead us to identify the origin of lentiviruses that cause AIDS in humans. The pathogenic potential and species specificity of SIVagm and SIVmac will be examined in homologous and heterologous monkey species. These analyses will direct us to search for viral and /or host factors important for pathogenesis. If the viral factors prove to be important attempts will be made to locate pathogenic determinants by generating hybrid viruses; replacing genes or regions of the non-pathogenic strains with that of the pathogenic ones. If all attempts to establish viral factor being important to pathogenesis have failed then we may have to conclude that host factors are important. Attempts will then be made to identify differences in target cells, define host responses and other genetic factors in the hosts.