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. Objective: To provide further understanding on the immunological and genetic basis of control of AIDS virus replication. 1. PROGRESS AND CONCERNS The SIV Elite Controller Resource was a new addition to the current WNPRC base grant to provide further understanding on the immunological and genetic basis of control of AIDS virus replication. These findings should help inform future HIV vaccine design. As in HIV-infected humans, a limited number of macaques spontaneously control SIV replication to a viral set point of less than 1,000 copies/ml after infection (""""""""Elite Controllers"""""""";ECs). This is a greater than two log reduction from the typical plasma virus load after challenge with SIVmac239. Throughout our studies, we have identified a number of ECs in a cohort of 200 Indian rhesus macaques. Genotyping for MHC class I alleles revealed that fourteen of these sixteen ECs expressed either Mamu-B*17 or Mamu-B*08. Interestingly, Mamu-B*08 appears to be the macaque functional equivalent of the human EC allele, HLA-B27. To increase the utility of these valuable animals, we are in the process of establishing a sample bank, database, and to house existing and future EC macaques at the WNPRC. Making these unique resources available to the community of investigators working on SIV would be an extremely valuable service to the field at large. In this first year of the SIV Elite Controller Resource, we currently have 10 SIV-infected macaques housed that at one time controlled SIV replication. Six of the ten animals currently have viral loads 1,000 vRNA copies/ml and in many cases are undetectable. The remaining 4 have viral loads higher than the definition of """"""""elite control"""""""" and are upwards of 100,000 vRNA copies/ml. These animals are equally intriguing in hopes of investigating what caused the loss of control in these animals. As part of the EC resource, we have transformed B-lymphoblastoid cell lines (BLCL) generated for each of these animals. These immortalized BLCL lines provide a renewable source of genomic DNA and mRNA from the animals even after death. These samples can be used to perform detailed immunogenetics analysis in the future as typing technologies continue to advance. We also regularly obtain blood samples to monitor the viral loads and to bank away frozen plasma and PBMC. In addition, to the animals currently housed on the SIV EC resource, we have identified at least 3 other SIV-infected from recent studies that are now classified as elite controllers. We will continue to monitor these animals as we have done for previous ECs. Records are kept on a variety of parameters on these SIV-infected macaques through the WNPRC colony records as well as an in house database. Through this web interface, users can obtain longitudinal data that includes SIV viral loads, lymphocyte subset analysis, hematology reports, blood draw history, and a variety of other pieces of pertinent information on a given animal of interest. We have also been in collaboration with the Colony Management and Genetics Services at the WNPRC to breed macaques that express Mamu-B*08 and Mamu-B*17, the two alleles tightly associated with control of SIV replication. In the period of 2008 to the beginning of 2009, 62 animals were born and genotyped. Of these 62 animals, 24 (39%) of the macaques expressed either Mamu-B*08 or Mamu-B*17. The increase in the frequency of Mamu-B*08 was extremely encouraging. The WNPRC frequency of Mamu-B*08+ macaques is ~7%. However, 20.9% of the 62 macaque babies express Mamu-B*08. In 2009, there have already been 34 direct breeding for Mamu-B*08 and 40 directed bleedings for Mamu-B*17 for animals slated to be born in this upcoming year. 2. ALLOCATION OF RESOURCE ACCESS A central mission of SIV Elite Controller Resource is to provide access to archived samples from SIV-infected EC macaques for retrospective analysis to AIDS research conducted at the Primate Center by WNPRC or outside investigators. At the current time, banked samples are primarily provided to AIDS researchers based at UW. However, the opportunity to utilize this resource on a broader scale exists with future projects with current collaborators. 3. DISSEMINATION We request that projects utilizing the SIV Elite Controller Resource acknowledge the WNPRC base grant in manuscripts and presentations. A number of manuscripts and reviews have already been published involving SIV EC macaques supported by this resource.
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