Distinct Plasma Concentrations of Acyl-CoA-Binding Protein (ACBP) in HIV Progressors and Elite Controllers.

Stéphane Isnard,Mohamed El-Far,Jean-Pierre Routy,John Lin,Guido Kroemer,Sanket Kant,Cécile L Tremblay,Carolina Berini,Madeleine Durand,Nicole F Bernard,Léna Royston,Brandon Fombuena,Tsoarello Mabanga,Simeng Bu

doi:10.3390/v14030453

Abstract

HIV elite controllers (ECs) are characterized by the spontaneous control of viral replication, and by metabolic and autophagic profiles which favor anti-HIV CD4 and CD8 T-cell responses. Extracellular acyl coenzyme A binding protein (ACBP) acts as a feedback inhibitor of autophagy. Herein, we assessed the circulating ACBP levels in ECs, compared to people living with HIV (PLWH) receiving antiretroviral therapy (ART) or not. We found lower ACBP levels in ECs compared to ART-naïve or ART-treated PLWH (p < 0.01 for both comparisons), independently of age and sex. ACBP levels were similar in ECs and HIV-uninfected controls. The expression of the protective HLA alleles HLA-B*27, *57, or *58 did not influence ACBP levels in ECs. ACBP levels were not associated with CD4 or CD8 T-cell counts, CD4 loss over time, inflammatory cytokines, or anti-CMV IgG titers in ECs. In ART-treated PLWH, ACBP levels were correlated with interleukin (IL)-1β levels, but not with other inflammatory cytokines such as IL-6, IL-8, IL-32, or TNF-α. In conclusion, ECs are characterized by low ACBP plasma levels compared to ART-naïve or ART-treated PLWH. As autophagy is key to anti-HIV CD4 and CD8 T-cell responses, the ACBP pathway constitutes an interesting target in HIV cure strategies.

Highlights

The recent description of the Esperanza patient who achieved a possible spontaneous HIV sterilizing cure represents a beacon of hope for people living with HIV (PLWH) [1,2,3,4].Elite controllers (ECs) can control HIV replication without antiretroviral therapy (ART) for a significant period of time
Blood samples were selected from PLWH who participated in the Canadian cohort of HIV-infected slow progressors (CIHR/Canadian HIV Trials Network (CTN) 247), and the HIV pathogenesis biobank [25]
Our study demonstrates that ECs have significantly lower plasma acyl-coA-binding protein (ACBP) levels compared to ART-naïve and ART-treated PLWH

Summary

Introduction

The recent description of the Esperanza patient who achieved a possible spontaneous HIV sterilizing cure represents a beacon of hope for people living with HIV (PLWH) [1,2,3,4].Elite controllers (ECs) can control HIV replication without antiretroviral therapy (ART) for a significant period of time. Our group has shown that the metabolic inputs of autophagy and lipophagy contribute to the HIV-specific CD4 and CD8 T-cell response in ECs [15,16]. Autophagy involves master regulators of cellular metabolism, such as the mammalian target of rapamycin (mTOR) and the 5 AMP-activated protein kinase (AMPK), combined with the selective removal of protein aggregates and organelles such as mitochondria, the endoplasmic reticulum, peroxisomes, lysosomes, and lipid droplets [18]. A form of selective autophagy, are regulated by different factors including acyl-coA-binding protein (ACBP). This protein, known as diazepam binding inhibitor (DBI), is involved in intracellular bioenergetic reactions and serves as an extracellular feedback inhibitor of autophagy [19,20,21]. ACBP can be considered a metabolic and neuroendocrine factor that regulates bioenergetic and cellular functions in a context-dependent manner [21,24]

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Conclusion