AI Article Synopsis

  • Persistence of HIV-1 latent reservoir cells during antiretroviral therapy (ART) presents a significant challenge in curing HIV-1.
  • * Researchers developed the "widely distributed intact provirus elimination" (WIPE) assay, a long-term cell culture system that mimics the diverse infection scenarios of HIV-1.
  • * The WIPE assay allows for the evaluation of latency-reversing agents (LRAs) and demonstrates that combining LRAs with ART can effectively reactivate and help eliminate latent HIV-1 cells.

Article Abstract

Persistence of HIV-1 latent reservoir cells during antiretroviral therapy (ART) is a major obstacle for curing HIV-1. Even though latency-reversing agents (LRAs) are under development to reactivate and eradicate latently infected cells, there are few useful models for evaluating LRA activity . Here, we establish a long-term cell culture system called the "widely distributed intact provirus elimination" (WIPE) assay. It harbors thousands of different HIV-1-infected cell clones with a wide distribution of HIV-1 provirus similar to that observed . Mathematical modeling and experimental results from this infection model demonstrates that the addition of an LRA to ART shows a latency-reversing effect and contributes to the eradication of replication-competent HIV-1. The WIPE assay can be used to optimize therapeutics against HIV-1 latency and investigate mechanistic insights into the clonal selection of heterogeneous HIV-1-infected cells.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017183PMC
http://dx.doi.org/10.1016/j.crmeth.2021.100122DOI Listing

Publication Analysis

Top Keywords

hiv-1 provirus
8
latency-reversing agents
8
wipe assay
8
hiv-1
5
distributed hiv-1
4
provirus elimination
4
elimination assay
4
assay evaluate
4
evaluate latency-reversing
4
agents persistence
4

Similar Publications

Tannic acid reactivates HIV-1 latency by mediating CBX4 degradation.

J Virol

December 2024

Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

HIV-1 can integrate viral DNA into host cell chromosomes and establish a long-term stable latent viral reservoir, a major obstacle in curing HIV-1 infection. The reactivation of latent proviruses with latency-reversing agents (LRAs) is a prerequisite for the eradication of viral reservoirs. Previous reports have shown that tannic acid (TA) exerts several biological functions, including antioxidant and antitumor activities.

View Article and Find Full Text PDF

Introduction: The main obstacle to achieving an HIV-1 cure is the proviral reservoir. To promote equity in HIV cure strategies, it is crucial to study the viral reservoir of the predominant HIV-1 subtype C in both women and men. Therefore, we investigated the dynamics of the (intact) viral reservoir in relation to plasma viral load (VL), CD4 T cell count, and immune activation before and during 96 weeks of successful antiretroviral therapy (ART).

View Article and Find Full Text PDF

CBP/p300 lysine acetyltransferases inhibit HIV-1 expression in latently infected T cells.

iScience

December 2024

Department of Biochemistry and Molecular Biology, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.

HIV-1 latency is regulated by chromatin modifying enzymes, and histone deacetylase inhibitors (HDACi) cause reactivation of provirus expression. Surprisingly, we observed that inhibitors of the CBP/p300 acetyltransferases also cause reversal of latency in T cells. CBP/p300 inhibitors synergize with various latency reversing agents to cause HIV-1 reactivation.

View Article and Find Full Text PDF

Despite effective treatment, Human immunodeficiency virus (HIV) persists in optimally treated people as a transcriptionally silent provirus. Latently infected cells evade the immune system and the harmful effects of the virus, thereby creating a long-lasting reservoir of HIV. To gain a deeper insight into the molecular mechanisms of HIV latency establishment, we constructed a series of HIV-1 fluorescent reporter viruses that distinguish active versus latent infection.

View Article and Find Full Text PDF

Elimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!