Arsenic Trioxide Impacts Viral Latency and Delays Viral Rebound after Termination of ART in Chronically SIV-Infected Macaques

Advanced Science
Qing YangLing Chen

Abstract

The latent viral reservoir is the source of viral rebound after interruption of antiretroviral therapy (ART) and is the major obstacle in eradicating the latent human immunodeficiency virus-1 (HIV-1). In this study, arsenic class of mineral, arsenic trioxide, clinically approved for treating acute promyelocytic leukemia, is demonstrated to reactivate latent provirus in CD4+ T cells from HIV-1 patients and Simian immunodeficiency virus (SIV)-infected macaques, without significant systemic T cell activation and inflammatory responses. In a proof-of-concept study using chronically SIVmac239-infected macaques, arsenic trioxide combined with ART delays viral rebound after ART termination, reduces the integrated SIV DNA copies in CD4+ T cells, and restores CD4+ T cells counts in vivo. Most importantly, half of arsenic trioxide-treated macaques show no detectable viral rebound in the plasma for at least 80 days after ART discontinuation. Mechanistically, the study reveals that CD4 receptors and CCR5 co-receptors of CD4+ T cells are significantly downregulated by arsenic trioxide treatment, which reduces susceptibility to infection after provirus reactivation. Furthermore, an increase in SIV-specific immune responses after arsenic trio...Continue Reading

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Citations

Oct 23, 2019·Frontiers in Immunology·Christina GavegnanoVincent C Marconi
Mar 12, 2020·The EMBO Journal·Iart Luca ShytajMarina Lusic
Mar 13, 2020·Metallomics : Integrated Biometal Science·Qian Qian WangHua Naranmandura
Oct 19, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Anatoly V SkalnyAlexey A Tinkov
Apr 4, 2021·Veterinary Sciences·Sabari Nath Neerukonda

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Methods Mentioned

BETA
acetylation
sumoylation
flow cytometry
PCR
PMA
Assay
density gradient centrifugation

Software Mentioned

FlowJo
GraphPad
GraphPad Prism

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