PATHOGENESIS OF NATURAL SIV AND STLV INFECTIONS IN HUMANS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的总体目标是评估喀麦隆感染猴免疫缺陷病毒的人中出现新的艾滋病毒群体的风险。已经确定的是，HIV-1是通过SIV在黑猩猩（cpz）中的跨物种传播而出现的，人类通过狩猎、准备丛林肉或家庭宠物而暴露于SIV。 我们的假设是，SIVcpz人类感染有一个低的内在致病性后，直接跨物种传播的自然黑猩猩宿主到人类。这些原发性SIV感染不会在人与人之间传播，其传播水平不足以维持新的流行病群的出现，与HIV-1 M、O群或HIV-2 A和B群相当。 该假说预测，SIVcpz将复制到显着的水平，在急性人类感染，但将在慢性阶段得到控制。喀麦隆的项目负责人将协调和监督一个小组，对喀麦隆西南部讲英语的普通人群进行SIV感染筛查。 将采集血液并用于抗体测定，以检测SIVcpz和其他SIV毒株。我们还将采用基于PCR的检测和基因组测序来识别SIV的特定毒株。一些测试将在现场进行，但大多数实验室工作将在送往美国的标本上进行。 在确定SIV感染者后，我们将描述喀麦隆人类SIV感染的流行病学和自然史。将对接触者进行测试，以确定这些猿类逆转录病毒是否能够在人类之间传播。这些人类感染的结局也将在临床上得到解决。对SIV抗体阳性者进行反复临床随访。到目前为止，人类的SIV样感染被认为是短暂的感染，但这还没有得到广泛的研究，这是本项目的目标。 为了实现我们的目标，喀麦隆的研究小组将收集关于整个人口样本的基本流行病学信息以及他们过去接触SIV的简要历史  例如猎杀猴子和接触家养宠物。我们的目标是在4年内收集大约16，000份血液样本，我们预计其中将检测到大约40名SIV感染者。对于这40人的小组，我们将跟进详细评估他们将SIV感染传播给其他人的潜在风险因素  包括家庭接触（如共用餐具、剃须用具、牙刷）、性接触、母婴接触、仪式性切割/划痕和医疗史  尤其是与血液传播病毒有关的侵入性操作  例如注射、手术和输血。 该项目于2009年9月获得资助。 正在对国内项目负责人进行审查。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective of the project is to assess the risk of emergence of new HIV groups from simian immunodeficiency virus (SIV) - infected persons in Cameroon. It is well established that HIV-1 emerged through cross-species transmission of SIV in chimpanzees (cpz) to humans who were exposed through hunting, preparation of bush meat or household pets. Our hypothesis is that SIVcpz human infections have a low intrinsic pathogenicity after direct cross-species transmission from the natural chimpanzee hosts to humans. These primary SIV infections do not spread from person to person at a level sufficient to sustain the emergence of new epidemic groups, comparable to HIV-1 groups M, O or HIV-2 groups A and B. The hypothesis predicts that SIVcpz will replicate to significant levels during acute human infections but will be controled in the chronic stage. The project head in Cameroon will coordinate and oversee a team for screening the general human population in Southwest anglophone Cameroon for SIV infections. Blood will be collected and used for antibody assays to detect SIVcpz and other strains of SIV. We will also employ PCR-based testing and genome sequencing to identify particular strains of SIV. Some testing will be done on sight, but the majority of laboratory work will be done on specimens sent to the USA. After identifying persons with SIV infections, we will characterize the epidemiology and natural history of SIV infections in humans in Cameroon. Contacts will be tested to determine if these simian retroviruses are capable of transmissible between humans. The outcome of these infections in humans will be also clinically addressed. SIV antibody positive persons will have repeated clinical follow-ups. Thus far, SIV-like infections in humans are believed to be transient infections, but this has not been extensively studied and is the goal of this project. To accomplish our aims, the team in Cameroon will collect basic epidemiological information about the entire population sample and a brief history of their past exposure to SIV  e.g. hunting and butchering monkeys and contact with household pets. The goal is to collect approximately 16,000 blood samples over 4 years, of which we anticipate detecting approximately 40 SIV infected humans. For this group of 40, we will follow up with a detailed assessment of potential risk factors for transmission of their SIV infections to other humans  including household exposure (e.g. sharing utensils, shaving gear, toothbrushes), sexual contacts, mother-to-child, ritual cutting/scarification, and histories of medical care  especially invasive procedures associated with transmission of blood borne viruses  e.g. injections, surgery, and blood transfusions. This project was funded in September 2009. Searches are in progress for an in-country project head.