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: 7937013
• 负责人: Preston A Marx
• 金额: $ 64.83万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937013
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Africa; African; American; Antibodies; Biological Assay; Blood; Blood Cells; Blood Transfusion; Blood specimen; Cameroon; Caring; Child; Chronic; Clinic; Clinical; Critiques; Data; Documentation; Enzyme-Linked Immunosorbent Assay; Epidemic; Epidemiology; Exposure to; Fever; Funding; Goals; HIV; HIV-1; HIV-2; Household; Human; Infection; Injection of therapeutic agent; Knowledge; Life; Macaca mulatta; Medical History; Modeling; Molecular Cloning; Monkeys; Mothers; Natural History; Operative Surgical Procedures; Outcome; Pathogenesis; Pathogenicity; Peptides; Persons; Phylogenetic Analysis; Plant Roots; Population; Populations at Risk; Prevalence; Procedures; Property; Recording of previous events; Retroviridae; Risk; Risk Factors; Ritual compulsion; SIV; Sampling; Sierra Leone; Source; Staging; Testing; Toothbrushing; Virus; Western Blotting; Work; base; follow-up; nonhuman primate; novel strategies; pet animal; prevent; public health relevance; simian virus; toothbrush; transmission process

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.

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 HIV 类型的风险。这一目标将通过使用一种新策略来检测自然感染 SIV 的人、描述他们的感染特征并检测其接触者的感染情况来实现。性接触和因果接触都将被研究。最近在英语国家喀麦隆使用 SIV 检测进行的初步研究证实了这一项目的可行性。我们对喀麦隆昆巴及其附近诊所的 1536 名人员进行了测试，其中大部分是发烧和其他急性疾病。我们对所有阳性和不确定结果使用蛋白质印迹法，然后使用 SIV 特异性 SIV 肽 ELISA。这种新方法确定了 6 名具有 SIV 抗体的人，其中 1 名 SIVcpz、1 名 SIVagm 以及各 2 名 SIVrcm 和 SIVmnd。目标 1. 对喀麦隆西南部的一般人群进行 S​​IV 感染筛查。我们将使用已在该地区得到验证的抗体检测。我们还将采用基于 PCR 的测试。目标 2. 表征从喀麦隆人体内分离或扩增的 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. 描述接触猿猴病毒的人类中 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。将对接触者进行测试，以确定这些逆转录病毒是否可以在人与人之间传播。这些人类感染的后果将得到解决。 SIV抗体+者将进行重复的临床随访。迄今为止，人类的 SIV 样感染一直是死胡同。这种方法将使我们能够发现和追踪 SIV 人类感染，以评估新艾滋病毒出现的风险。法国和美国的其他团体也在喀麦隆开展工作，但这些病毒的血清流行率相对较低，因此需要资助其他团体来增加在急性阶段发现活动性 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，尽管这一知识对于防止新流行病的出现至关重要。尽管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，但我们不知道为何在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。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。