PATHOGENESIS OF NATURAL SIV AND STLV INFECTIONS IN HUMANS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该项目的总体目标是评估喀麦隆和刚果共和国的猴免疫缺陷病毒感染者出现新的艾滋病毒群体的风险。众所周知，HIV-1是通过在黑猩猩(CPZ)中跨物种传播SIV而出现的，这些人通过狩猎、准备丛林肉或家养宠物接触到艾滋病毒。 我们的假设是，SIVcpz人类感染从自然黑猩猩宿主直接跨物种传播到人类后，内在致病性较低。这些主要的SIV感染在人与人之间传播的程度不足以维持新的流行群体的出现，可与艾滋病毒-1 M、O组或艾滋病毒-2 A和B组相媲美。 该假说预测，在急性人类感染期间，SIVcpz将复制到显着水平，但在慢性阶段将受到控制。喀麦隆和刚果的项目负责人将协调和监督一个小组，对喀麦隆和刚果西南部以英语为母语的普通人口进行SIV感染筛查。重点将放在血库样本上，该项目将在那里获得艾滋病毒+和艾滋病毒不确定样本。血液将用于抗体检测，以检测SIVcpz和其他SIV毒株。我们还将使用基于聚合酶链式反应的测试和基因组测序来识别特定的SIV菌株。一些检测将在喀麦隆即期进行，但大部分实验室工作将在被送往美国的标本上完成。刚果的实验室为国内进行的分析提供了更好的设备。 在确定SIV感染者之后，我们将描述人类感染SIV的流行病学和自然病史。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与人之间传播。这些感染对人类的后果也将在临床上得到解决。SIV抗体阳性者将进行反复的临床随访。到目前为止，人类中的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，这也是本项目的目标。 为了实现我们的目标，喀麦隆和刚果的团队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，例如狩猎和屠宰猴子以及与家养宠物的接触。我们的目标是在4年内检测大约16,000到20,000个血液样本，其中我们预计检测到大约40个感染SIV的人。对于这40人，我们将对他们感染SIV病毒传播给其他人的潜在风险因素进行详细评估，包括家庭接触(例如共用餐具、剃须用具、牙刷)、性接触、母婴接触、仪式切割/划痕以及医疗历史，特别是与血液传播病毒传播相关的侵入性程序，如注射、手术和输血。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 and the Republic of Congo. 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 controlled in the chronic stage. The project heads in Cameroon and the Congo will coordinate and oversee a team for screening the general human population in Southwest anglophone Cameroon and the Congo for SIV infections. The focus will be on blood bank specimens where the project will have access to HIV+ and HIV indeterminant samples. Blood will be 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 in Cameroon, but the majority of laboratory work will be done on specimens sent to the USA. The Laboratories in Congo are better equipped for in country conducted assays. After identifying persons with SIV infections, we will characterize the epidemiology and natural history of SIV infections in humans. 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 teams in Cameroon and Congo 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 test approximately 16,000 to 20,000 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.