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感染者出现新的HIV类型的风险。这一目标将通过采用一种新的战略来实现，即对自然感染SIV的人进行检测，确定其感染特征，并检测其接触者的感染情况。将研究性接触和因果接触。最近，在讲英语的喀麦隆，利用SIV检测法进行的初步研究确定了这一项目的可行性。我们测试了1536人在昆巴和附近的诊所，喀麦隆的任何原因，主要是发烧和其他急性疾病。我们对所有阳性和不确定性结果使用蛋白质印迹法，然后使用SIV特异性SIV肽ELISA。这种新的方法鉴定出6人具有SIV抗体，1人具有SIVcpz，1人具有SIVagm，2人具有SIVrcm和SIVmnd。目标1.在喀麦隆西南部的一般人群中筛查SIV感染。我们将使用已在该地区验证的抗体检测。我们还将采用基于PCR的测试。目标2.描述从喀麦隆人类分离或扩增的SIV的病毒学和系统发育特性。例如，我们将测试G->A超突变以测试SIV对人类的适应性。目标3.描述暴露于猴病毒的人类SIV感染的流行病学和自然史。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在人类之间传播。将讨论这些感染在人类中的结果。SIV抗体阳性者将重复进行临床随访。到目前为止，人类的SIV样感染一直是死胡同感染。这种方法将使我们能够发现和跟踪SIV人类感染，以评估新的HIV出现的风险。法国和美国的其他小组正在喀麦隆工作，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，以增加发现急性期活动性SIV感染的机会。公共卫生相关性：艾滋病病毒出现的根本原因仍然不明，尽管这一知识对于防止新的流行病的出现至关重要。虽然非洲的猿免疫缺陷病毒（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突然出现并成为世纪流行的人类艾滋病病毒却一无所知。该项目将追踪人类SIV感染的自然史，以了解艾滋病流行是如何开始的。

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.