Human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) and is responsible for a devastating pandemic infecting around 38 million people worldwide. Despite the remarkable efficacy of antiretroviral therapy (ART) that turned the deadly disease into a manageable condition, the infection is uncurable due to the persistence of latent viral forms in a small population of latently infected CD4+ T cells. This represents the major barrier to a cure. A latent reservoir is characterized by stably integrated, replication-competent intact proviruses repressed by a plethora of interconnected silencing cellular and viral mechanisms operating at epigenetic, transcriptional, and post-transcriptional levels. Moreover, the integration site of the virus, its genomic location and spatial positioning in the nucleus as well as the transcriptional program of the host cell influence HIV latency establishment and maintenance.
The “shock-and-kill” strategy is one of the most explored HIV-1 cure approaches to eliminate latent reservoirs. However, so far, current clinical trials of the “shock-and-kill” strategy using latency-reversing agents (LRAs) to reactivate the virus for the subsequent elimination of the latent reservoir by immune clearance or viral cytopathic effects have been disappointing with no significant impact on the HIV reservoir size. Determinants such as the heterogeneity of the latent reservoirs and the complexity of epigenetic, transcriptional, and post-transcriptional molecular mechanisms regulating HIV-1 latency largely contribute to the limited success of the “shock-and-kill” strategy. Therefore, if a “shock-and-kill” strategy is ever going to be successful, a better understanding of molecular mechanisms underlying HIV latency and reactivation that are driven by virus-host interactions is pivotal in designing more potent approaches to hopefully reach a cure.
This Research Topic in Frontiers in Cellular and Infection Microbiology welcomes Reviews and Original Research articles that explore and discuss molecular mechanisms contributing to HIV-1 latency and reactivation from latency, with a special emphasis on the virus-host interplay.
Key topics should describe molecular mechanisms relevant for the establishment of HIV latency and their impact on viral reactivation. These key topics can include, but are not limited to:
• The integration site of the virus and the role of chromatin environment;
• Mechanisms of transcriptional interference;
• Role of cellular inducible transcription initiation factors;
• Epigenetic control of HIV-1 transcription;
• Role of Tat, P-TEFb and Tat post-translational modifications;
• Post-transcriptional molecular mechanisms of HIV gene expression and latency;
• Epitranscriptomic regulation of HIV gene expression;
• Role of long noncoding RNA in HIV latency and reactivation;
• Mechanisms of HIV persistence in myeloid/non-T-cell reservoirs.
Topic Editor Alexander Pasternak received research funding from Gilead Sciences, Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) and is responsible for a devastating pandemic infecting around 38 million people worldwide. Despite the remarkable efficacy of antiretroviral therapy (ART) that turned the deadly disease into a manageable condition, the infection is uncurable due to the persistence of latent viral forms in a small population of latently infected CD4+ T cells. This represents the major barrier to a cure. A latent reservoir is characterized by stably integrated, replication-competent intact proviruses repressed by a plethora of interconnected silencing cellular and viral mechanisms operating at epigenetic, transcriptional, and post-transcriptional levels. Moreover, the integration site of the virus, its genomic location and spatial positioning in the nucleus as well as the transcriptional program of the host cell influence HIV latency establishment and maintenance.
The “shock-and-kill” strategy is one of the most explored HIV-1 cure approaches to eliminate latent reservoirs. However, so far, current clinical trials of the “shock-and-kill” strategy using latency-reversing agents (LRAs) to reactivate the virus for the subsequent elimination of the latent reservoir by immune clearance or viral cytopathic effects have been disappointing with no significant impact on the HIV reservoir size. Determinants such as the heterogeneity of the latent reservoirs and the complexity of epigenetic, transcriptional, and post-transcriptional molecular mechanisms regulating HIV-1 latency largely contribute to the limited success of the “shock-and-kill” strategy. Therefore, if a “shock-and-kill” strategy is ever going to be successful, a better understanding of molecular mechanisms underlying HIV latency and reactivation that are driven by virus-host interactions is pivotal in designing more potent approaches to hopefully reach a cure.
This Research Topic in Frontiers in Cellular and Infection Microbiology welcomes Reviews and Original Research articles that explore and discuss molecular mechanisms contributing to HIV-1 latency and reactivation from latency, with a special emphasis on the virus-host interplay.
Key topics should describe molecular mechanisms relevant for the establishment of HIV latency and their impact on viral reactivation. These key topics can include, but are not limited to:
• The integration site of the virus and the role of chromatin environment;
• Mechanisms of transcriptional interference;
• Role of cellular inducible transcription initiation factors;
• Epigenetic control of HIV-1 transcription;
• Role of Tat, P-TEFb and Tat post-translational modifications;
• Post-transcriptional molecular mechanisms of HIV gene expression and latency;
• Epitranscriptomic regulation of HIV gene expression;
• Role of long noncoding RNA in HIV latency and reactivation;
• Mechanisms of HIV persistence in myeloid/non-T-cell reservoirs.
Topic Editor Alexander Pasternak received research funding from Gilead Sciences, Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
