Pathogenesis of Natural SIV and STLV Infections in Humans

描述(由申请人提供)：该项目的总体目标是评估喀麦隆SIV感染者出现新艾滋病毒类型的风险。为了实现这一目标，将采用一种新的战略，对自然感染SIV的人进行检测，确定他们的感染特征，并在他们的接触者中进行感染检测。性接触和因果接触都将被研究。最近在使用英语国家喀麦隆的SIV化验的初步研究中确定了这一项目的可行性。我们测试了1536名因任何原因在喀麦隆昆巴及其附近诊所就诊的人，主要是发烧和其他急性疾病。我们使用免疫印迹和SIV特异性SIV多肽ELISA对所有阳性和不确定结果进行检测。该方法鉴定出6例SIV抗体阳性者，1例SIVcpz抗体阳性者，1例SIVagm抗体阳性者，2例SIVrcm抗体阳性者和2例SIVmnd抗体阳性者。目的1.对喀麦隆西南部普通人群进行SIV感染筛查。我们将使用已经在该地区得到验证的抗体检测。我们还将采用基于聚合酶链式反应的检测。目的2.研究从喀麦隆人中分离或扩增的SIV的病毒学和系统发育特性。例如，我们将测试G-&gt；A超突变，以测试SIV是否适应人类。目的3.描述接触猿猴病毒的人群中SIV感染的流行病学和自然病史。我们将研究复制、传播和发病机制。将对接触者进行检测，以确定这些逆转录病毒是否可以在人与人之间传播。这些感染对人类的后果将得到解决。SIV抗体携带者将进行反复的临床随访。到目前为止，人类中的SIV样感染一直是死胡同。这种方法将使我们能够发现和跟踪SIV人类感染，以评估出现新HIV的风险。法国和美国的其他小组也在喀麦隆工作，但这些病毒的血清流行率相对较低，因此需要资助其他小组，以增加在急性阶段发现活跃的SIV感染的机会。与公共卫生相关：艾滋病病毒出现的根本原因仍然未知，尽管这一知识对于防止出现新的流行病至关重要。虽然非洲的猿猴免疫缺陷病毒(SIV)已被确定为艾滋病病毒的原始来源，但对于为什么两种不同的SIV在20世纪突然出现成为流行的人类艾滋病病毒，人们尚不清楚。这个项目将追踪人类感染SIV的自然历史，以了解艾滋病疫情是如何开始的。

DESCRIPTION (provided by applicant): The overall objective of this project is to assess the risk of emergence of new HIV types from SIV-infected persons in Cameroon. This objective will be obtained by using a new strategy for testing for persons naturally infected with SIV, characterizing their infections and testing for infection in their contacts. Both sexual and causal contacts will be studied. The feasibility of such a project was recently established in preliminary studies using SIV assays in Anglophone Cameroon. We tested 1536 persons attending clinics in and near Kumba, Cameroon for any reason, mostly fevers and other acute illnesses. We used western blots followed by SIV-specific SIV peptide ELISA on all positive and indeterminants results. This new approach identified 6 persons with SIV antibody, 1 SIVcpz, 1 SIVagm and 2 each for SIVrcm and SIVmnd. Aim 1. To screen the general human population in Southwest Cameroon for SIV infections. We will use antibody assays that have already been validated in this region. We will also employ PCR-based testing. Aim 2. To characterize the virologic and phylogenetic properties of SIV either isolated or amplified from humans in Cameroon. For example, we will test G->A hypermutation for testing for adaptation of SIV to humans. Aim 3. To characterize the epidemiology and natural history of SIV infections in humans exposed to simian viruses. We will examine replication, transmission and pathogenesis. Contacts will be tested to determine if these retroviruses are transmissible between humans. The outcome of these infections in humans will be addressed. SIV antibody + persons will have repeated clinical follow-ups. Thus far, SIV-like infections in humans have been dead end infections. This approach will enable us to find and track SIV human infections to assess the risk for emergence of new HIVs. Other groups both French and American are working in Cameroon, but the relatively low sero-prevalence for these viruses warrants other groups being funded to increase the chances of finding active SIV infections in the acute stage. PUBLIC HEALTH RELEVANCE: The root causes for the emergence of the AIDS viruses remain unknown even though this knowledge is vital to prevent the emergence of new epidemics. Although simian immunodeficiency viruses (SIVs) in Africa have been identified as the original source of the AIDS viruses, nothing is known as to why 2 different SIVs suddenly emerged to become epidemic human AIDS viruses in the 20th century. This project will trace the natural history SIV infections in humans to understand how the AIDS epidemic began.