PATHOGENESIS OF NATURAL SIV AND STLV INFECTIONS IN HUMANS

点击翻译按钮获取中文摘要

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.