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感染者出现新的艾滋病毒类型的风险。为实现这一目标，将采用一种新的战略，对自然感染SIV的人进行检测，确定其感染特征，并对其接触者进行感染检测。性接触和因果接触都将被研究。最近在喀麦隆英语国家使用SIV测定法进行了初步研究，确定了这样一个项目的可行性。我们对在喀麦隆昆巴及其附近的诊所就诊的1536人进行了检测，其中大多数是发烧和其他急性疾病。我们使用western blots和SIV特异性SIV肽ELISA检测所有阳性和不确定结果。该方法鉴定出6例SIV抗体，SIVcpz 1例，SIVagm 1例，SIVrcm和SIVmnd各2例。目的1。对喀麦隆西南部一般人群进行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pcr的检测。目标2。描述从喀麦隆人身上分离或扩增的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。研究猴免疫缺陷病毒暴露人群感染的流行病学特征和自然历史。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与人之间传播。将处理这些人类感染的后果。SIV抗体阳性者将进行反复的临床随访。到目前为止，人类的siv类感染都是死端感染。这种方法将使我们能够发现和跟踪SIV人类感染，以评估出现新的艾滋病毒的风险。法国和美国的其他研究小组也在喀麦隆开展工作，但由于这些病毒的血清患病率相对较低，其他研究小组有理由得到资助，以增加在急性期发现活动性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未知，尽管这方面的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，但对于为什么在20世纪突然出现两种不同的siv成为流行的人类艾滋病病毒却一无所知。该项目将追踪人类SIV感染的自然历史，以了解艾滋病的流行是如何开始的。

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.