WNPRC ELITE CONTROLLER RESOURCE

University Of Wisconsin-Madison, Madison WI

Investigators

Linked publications & trials

Abstract

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. 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. 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. 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. We have 37 SIV-infected macaques that at one time controlled SIV replication. 6 of these animals were infected with SIVsmmE660, the remaining 31 were infected with either wild type or a mutant version of SIVmac239 virus. We have accumulated more than 7,000 sample vials from these animals. The samples include plasma, serum, PBMC, and B-LCL. 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. 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, samples are primarily used by AIDS researchers of the UW-Madison. However, recently we have created a website (http://www.primate.wisc.edu/ec/) to invite other investigators to use this sample bank. 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 have already been published involving SIV EC macaques supported by this resource. PUBLICATIONS: Vojnov L, Reed JS, Weisgrau KL, Rakasz EG, Loffredo JT, Piaskowski SM, Sacha JB, Kolar HL, Wilson NA, Johnson RP, Watkins DI. Effective simian immunodeficiency virus-specifici CD8+ T cells lack an easily detectable, shared characteristic. J Virol. 2010 Jan;84(2):753-64. PMID: 19889785 Loffredo JT, Sidney J, Bean AT, Beal DR, Bardet W, Wahl A, Hawkins OE, Piaskowski S, Wilson NA, Hildebrand WH, Watkins DI, Sette A. Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity. J Immunol. 2009 Jun 15;182(12):7763-75.PMID: 19494300. Sacha JB, Giraldo-Vela JP, Buechler MB, Martins MA, Maness NJ, Chung C, Wallace LT, Le[unreadable]n EJ, Friedrich TC, Wilson NA, Hiraoka A, Watkins DI. Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9791-6. PMID: 19478057 PMCID: PMC2687996