CTD kinases are critical for the elongation of HIV transcription and co-transcriptional processing of viral transcripts. They function after chromatin remodeling and before translation of viral proteins. Thus, our project will interface well with those of Greene, Ott and Verdin on epigenetic regulation ofthe integrated provirus. Manipulations that change the HIV epigenome will then be evaluated with respect to their effects on CTD kinases, for which we not only have the reagents but also a greater understanding of their function. It is more than likely that high throughput screens in these other projects will identify compounds that will affect P-TEFb, CycK or CycL complexes, or that will act in concert with agonists that affect primarily these CTD kinases'. In addition, studies by Karn on effects of cellular signaling on P-TEFb and NF-kB will allow us to his latency model to test our ideas on CycK and CycL complexes as well. It is also possible that effects of Nef are not mediated via P-TEFb but rather disregulate subunits of CycK, By differentially affecting HIV splicing and polyadenylation, they might allow more cells to enter proviral latency.
The projects in mouse and macaque models in the HIV Collaboratory will directly contribute to several Important objectives ofthe Collaboratory including identification of the range of cells and tissues harboring latent proviruses, dissection of molecular mechanisms underlying HIV latency, and discovery and evaluation of new compounds and strategies for successfully purging the virus from the latent reservoirs or establishing a drug-free remission.
|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; NiubÃ³, 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|
Showing the most recent 10 out of 187 publications