PATHOGENESIS OF NATURAL SIV AND STLV INFECTIONS IN HUMANS

人类自然 SIV 和 STLV 感染的发病机制

• 批准号: 8358130
• 负责人: Preston A Marx
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358130
• 关键词: Acute; Address; Antibodies; Biological Assay; Blood; Blood Banks; Blood Transfusion; Blood specimen; Cameroon; Caring; Child; Chronic; Clinical; Congo; Country; Epidemic; Epidemiology; Exposure to; Funding; Goals; Grant; HIV; HIV-1; HIV-2; Head; Household; Human; Infection; Injection of therapeutic agent; Laboratories; Meat; Medical History; Monkeys; Mothers; National Center for Research Resources; Natural History; Operative Surgical Procedures; Outcome; Pan Genus; Pathogenesis; Pathogenicity; Persons; Population; Preparation; Primates; Principal Investigator; Procedures; Recording of previous events; Research; Research Infrastructure; Resources; Risk; Risk Factors; Ritual compulsion; SIV; Sampling; Screening procedure; Simian Retroviruses; Source; Specimen; Staging; Testing; Toothbrushing; United States National Institutes of Health; Virus; Virus Diseases; Vision; Work; base; cost; follow-up; genome sequencing; pet animal; toothbrush; transmission process

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 该项目的总体目的是评估来自SIMIAN免疫缺陷病毒（SIV）的新艾滋病毒群体的风险，即喀麦隆和刚果共和国的感染者。众所周知，HIV-1是通过黑猩猩（CPZ）的跨物种传播到通过狩猎，制备灌木肉或家宠物而暴露的人类中出现的。 我们的假设是，在直接跨物种从天然黑猩猩宿主传播到人类之后，SIVCPZ人类感染的内在致病性低。这些原发性SIV感染并未以足以维持新流行病组的出现的水平，与HIV-1组M，O或HIV-2组A和B组相提并论。 该假设预测，SIVCPZ将在急性人类感染期间复制至显着水平，但会在慢性阶段进行控制。喀麦隆和刚果的项目负责人将协调和监督一个团队，以筛查西南英语喀麦隆的一般人口和SIV感染的刚果。 重点将放在血库标本上，该标本将可以使用HIV+和HIV不确定样本。血液将用于检测SIVCPZ和其他SIV菌株的抗体测定。我们还将采用基于PCR的测试和基因组测序来识别特定的SIV菌株。将在喀麦隆进行一些测试，但大多数实验室工作将在发送给美国的标本上进行。刚果的实验室在国家进行的测定中可以更好地进行。 在识别患有SIV感染的人之后，我们将表征人类SIV感染的流行病学和自然史。将测试触点，以确定这些猿猴逆转录病毒是否能够在人之间传播。这些感染在人类中的结果也将在临床上解决。 SIV抗体阳性人员将重复进行临床随访。到目前为止，人们认为人类中的SIV样感染是短暂的感染，但尚未进行广泛的研究，并且是该项目的目标。 为了实现我们的目标，喀麦隆和刚果的团队将收集有关整个人口样本的基本流行病学信息以及他们过去对SIV的简短历史，例如狩猎和屠宰猴子，并与家养宠物接触。目的是在4年内测试大约16,000至20,000个血液样本，我们预计将检测到大约40个SIV感染的人。对于这组40人来说，我们将详细评估将其SIV感染传播到其他人类的潜在风险因素，包括家庭接触（例如共享餐具，剃须装备，牙刷），性接触，性接触，性接触，育儿，仪式削减/恐惧/恐惧/恐惧/恐惧和尤其是医疗保健的历史以及与血液传播的传播相关的医疗传播。注射，手术和输血。