The main objective of the Genomics Core will be to provide access to researchers on the collaborator to genomics technologies and the bioinformatic analysis needed to analyze the complex data derived from such technologies. Genomics technologies have become essential laboratory tools and will generate data that will guide the research in the collaboratory towards an HIV-1 cure. The Genomics Core will interact with every project in every objective and with the other cores proposed in the collaboratory. Specifically, with respect to virus genomics, the Genomics Core will provide access to sequencing, which will be used to identify the defects in proviral DNA that result in non-competent virus (Project 4.1) and will also be used to identify additional virus reservoirs by revealing viruses in the plasma whose sequence does not correlate with virus derived from the well-characterized CD4+ T cell reservoir (Project 4.2). Additionally, each project will benefit from the assays at the Genomics Core to monitor HIV replication in order to evaluate latency and the effects of HlV-inducing compounds. In respect to host genomics, the Genomics Core will primarily provide gene expression assays (whole genome microarray and qRT-PCR) in order to define the molecular mechanisms underlying viral persistence (Projects 1.1, 1.2,1.4 and 1.5) and determine biomarkers indicative of effective HlV-inducing compounds (Project 2.1). In addition, chromatin immunoprecipitation (ChIP) coupled with high throughput sequencing (ChlP-Seq) will be used to investigate gene regulation by the BAF chromatin remodeling complex (Project 1.2). When these studies are complete the genomics assays provided by the Genomics Core will have provided a better understanding of HIV latency, identified new pathways and avenues for therapeutic intervention, delineated the mode of action of HlV-inducing compounds, and characterized new viral reservoir in HIV-infected individuals.

Public Health Relevance

The experiments performed at the Genomics Core will use the latest technologies for analyzing virus and host genomes. The results of these experiments will accelerate research towards a cure for HIV-1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096113-04
Application #
8707358
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
City
Chapel Hill
State
NC
Country
United States
Zip Code
Davis, Zachary B; Cogswell, Andrew; Scott, Hamish et al. (2016) A Conserved HIV-1-Derived Peptide Presented by HLA-E Renders Infected T-cells Highly Susceptible to Attack by NKG2A/CD94-Bearing Natural Killer Cells. PLoS Pathog 12:e1005421
Imaz, Arkaitz; Martinez-Picado, Javier; Niubó, Jordi et al. (2016) HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen. J Infect Dis 214:1512-1519
Honeycutt, Jenna B; Wahl, Angela; Baker, Caroline et al. (2016) Macrophages sustain HIV replication in vivo independently of T cells. J Clin Invest 126:1353-66
Tokarev, Andrey; Stoneham, Charlotte; Lewinski, Mary K et al. (2016) Pharmacologic Inhibition of Nedd8 Activation Enzyme Exposes CD4-Induced Epitopes within Env on Cells Expressing HIV-1. J Virol 90:2486-502
Victor Garcia, J (2016) Humanized mice for HIV and AIDS research. Curr Opin Virol 19:56-64
Smith, Davey M; Nakazawa, Masato; Freeman, Michael L et al. (2016) Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment. Clin Infect Dis 63:1517-1524
Gianella, Sara; Anderson, Christy M; Var, Susanna R et al. (2016) Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection. J Virol 90:3944-52
Garcia, J Victor (2016) In vivo platforms for analysis of HIV persistence and eradication. J Clin Invest 126:424-31
Lee, Sook-Kyung; Zhou, Shuntai; Baldoni, Pedro L et al. (2016) Quantification of the Latent HIV-1 Reservoir Using Ultra Deep Sequencing and Primer ID In A Viral Outgrowth Assay. J Acquir Immune Defic Syndr :
Wagner, Gabriel A; Chaillon, Antoine; Liu, Siqi et al. (2016) HIV-associated neurocognitive disorder is associated with HIV-1 dual infection. AIDS 30:2591-2597

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