The Immunology Core primarily provides support for Project 1 and Project 3. For these projects, pigtail macaques will be infected with SHIV, with some then receiving various treatments intended to control viral replication and influence the viral reservoir. The Core will longitudinally measure the SHIV-specific CD4+ and CD8+ T cells in the blood of these animals at different stages in the treatment regimens. These measurements will be made using a flow cytometric intracellular cytokine staining (ICS) assay. For this assay, peripheral blood mononuclear cells (PBMC) are stimulated ex vivo for 6 hours with pools of overlapping 15-mer peptides that match the sequence of the HIV/SIV proteins encoded by the virus used to infect the monkeys. Depending on the amount of PBMC available at each time point, responses to all SHIV-encoded proteins or only selected proteins will be examined. This is a multi-parametric assay that measures multiple cytokines as well as memory markers;therefore, we can measure both the magnitude and the character or quality of the response. Many groups have published reports proposing associations between effective or non-effective T-cell responses and particular functional or phenotypic profiles. Thus, a detailed characterization of the T-cell responses that are gained or lost subsequent to the treatment interventions in these projects will be informative for correlating with treatment outcome.
These projects will study treatment modalities aimed at decreasing the HIV reservoir. The Immunology Core will determine the effect of these treatments on the immune system, particularly the T-cell component. This is useful not only for monitoring the effectiveness of these treatments, but also for describing the type of T-cell response that may be useful to diagnostically monitor HIV disease and treatment.
|Cannon, Paula M; Kohn, Donald B; Kiem, Hans-Peter (2014) HIV eradication--from Berlin to Boston. Nat Biotechnol 32:315-6|
|Boissel, Sandrine; Jarjour, Jordan; Astrakhan, Alexander et al. (2014) megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Nucleic Acids Res 42:2591-601|
|Younan, Patrick; Kowalski, John; Kiem, Hans-Peter (2014) Genetically modified hematopoietic stem cell transplantation for HIV-1-infected patients: can we achieve a cure? Mol Ther 22:257-64|
|Baxter, Sarah K; Scharenberg, Andrew M; Lambert, Abigail R (2014) Engineering and flow-cytometric analysis of chimeric LAGLIDADG homing endonucleases from homologous I-OnuI-family enzymes. Methods Mol Biol 1123:191-221|
|Weber, Nicholas D; Aubert, Martine; Dang, Chung H et al. (2014) DNA cleavage enzymes for treatment of persistent viral infections: recent advances and the pathway forward. Virology 454-455:353-61|
|Matrajt, Laura; Younan, Patrick M; Kiem, Hans-Peter et al. (2014) The majority of CD4+ T-cell depletion during acute simian-human immunodeficiency virus SHIV89.6P infection occurs in uninfected cells. J Virol 88:3202-12|
|Kuhar, Ryan; Gwiazda, Kamila S; Humbert, Olivier et al. (2014) Novel fluorescent genome editing reporters for monitoring DNA repair pathway utilization at endonuclease-induced breaks. Nucleic Acids Res 42:e4|
|Hall Sedlak, Ruth; Jerome, Keith R (2014) The potential advantages of digital PCR for clinical virology diagnostics. Expert Rev Mol Diagn 14:501-7|
|Sedlak, Ruth Hall; Jerome, Keith R (2013) Viral diagnostics in the era of digital polymerase chain reaction. Diagn Microbiol Infect Dis 75:1-4|
|Peterson, C W; Younan, P; Jerome, K R et al. (2013) Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART. Gene Ther 20:695-702|
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