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Activation of HIV-1 from Latent Infection via Synergy of RUNX1 Inhibitor Ro5-3335 and SAHA


Since it was first discovered in the early 1980s, Human Immunodeficiency Virus 1 (HIV-1), the causative agent of Acquired Immunodeficiency Syndrome (AIDS), has been the focus of intense research. In untreated individuals, the number of CD4+ T-cells in the blood slowly drops over time and the patient eventually succumbs to an opportunistic infection. Although current therapies are capable of managing the virus; they do not represent a true cure. As a retrovirus, HIV-1 incorporates itself into the host genome and survives in the long-lived population of memory T-cells found in the human host. In this study, we examine the roll of a T-cell specific transcription factor (RUNX1) in the control of HIV-1 replication. Through various molecular studies, we show that RUNX1 represses HIV-1 replication in T-cells. By examining samples from patients with HIV-1, we are able to show a negative correlation between viral replication and RUNX1 expression. Finally, we show that an inhibitor of RUNX1 synergizes with Vorinostat, a current lead compound in the quest to re-active HIV-1 and purge the latent pool.


Vyšlo v časopise: Activation of HIV-1 from Latent Infection via Synergy of RUNX1 Inhibitor Ro5-3335 and SAHA. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003997
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003997

Souhrn

Since it was first discovered in the early 1980s, Human Immunodeficiency Virus 1 (HIV-1), the causative agent of Acquired Immunodeficiency Syndrome (AIDS), has been the focus of intense research. In untreated individuals, the number of CD4+ T-cells in the blood slowly drops over time and the patient eventually succumbs to an opportunistic infection. Although current therapies are capable of managing the virus; they do not represent a true cure. As a retrovirus, HIV-1 incorporates itself into the host genome and survives in the long-lived population of memory T-cells found in the human host. In this study, we examine the roll of a T-cell specific transcription factor (RUNX1) in the control of HIV-1 replication. Through various molecular studies, we show that RUNX1 represses HIV-1 replication in T-cells. By examining samples from patients with HIV-1, we are able to show a negative correlation between viral replication and RUNX1 expression. Finally, we show that an inhibitor of RUNX1 synergizes with Vorinostat, a current lead compound in the quest to re-active HIV-1 and purge the latent pool.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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