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Translational Medical Research Commons™
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Articles 1 - 3 of 3
Full-Text Articles in Translational Medical Research
Hiv-1 Persistence In The Cns: Mechanisms Of Latency, Pathogenesis And An Update On Eradication Strategies., Shilpa Sonti, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Hiv-1 Persistence In The Cns: Mechanisms Of Latency, Pathogenesis And An Update On Eradication Strategies., Shilpa Sonti, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Center for Translational Medicine Faculty Papers
Despite four decades of research into the human immunodeficiency virus (HIV-1), a successful strategy to eradicate the virus post-infection is lacking. The major reason for this is the persistence of the virus in certain anatomical reservoirs where it can become latent and remain quiescent for as long as the cellular reservoir is alive. The Central Nervous System (CNS), in particular, is an intriguing anatomical compartment that is tightly regulated by the blood-brain barrier. Targeting the CNS viral reservoir is a major challenge owing to the decreased permeability of drugs into the CNS and the cellular microenvironment that facilitates the compartmentalization …
Combinatorial Use Of Both Epigenetic And Non-Epigenetic Mechanisms To Efficiently Reactivate Hiv Latency, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Combinatorial Use Of Both Epigenetic And Non-Epigenetic Mechanisms To Efficiently Reactivate Hiv Latency, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Center for Translational Medicine Faculty Papers
The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.
Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Center for Translational Medicine Faculty Papers
Latent HIV-1 proviruses are capable of reactivating productive lytic infection, but the precise molecular mechanisms underlying emergence from latency are poorly understood. In this study, we determined the contribution of the transcription factors NF-κB, NFAT, and AP-1 in the reactivation of latent HIV following T-cell receptor (TCR) activation using Jurkat T-cell clones harboring single latent HIV proviruses. Our findings demonstrate that during reactivation from latency, NF-κB enhances HIV transcription while NFAT inhibits it by competing with NF-κB for overlapping binding sites on the HIV long terminal repeat (LTR). We have also demonstrated for the first time the molecular contribution of …