Diurnal Variation of Plasma Extracellular Vesicle Is Disrupted in People Living with HIV.

Wilfried Wenceslas Bazié,Debashree Chatterjee,Michel Alary,Petronela Ancuta,Jean-Pierre Routy,Caroline Gilbert,Benjamin Goyer,Julien Boucher,Yuwei Zhang,Delphine Planas

doi:10.3390/pathogens10050518

Abstract

Background: Several types of extracellular vesicles (EVs) secreted by various immune and non-immune cells are present in the human plasma. We previously demonstrated that EV abundance and microRNA content change in pathological conditions, such as HIV infection. Here, we investigated daily variations of large and small EVs, in terms of abundance and microRNA contents in people living with HIV (PLWH) receiving antiretroviral therapy (HIV+ART) and uninfected controls (HIV−). Methods: Venous blood samples from n = 10 HIV+ART and n = 10 HIV− participants were collected at 10:00 and 22:00 the same day. Large and small plasma EVs were purified, counted, and the mature miRNAs miR-29a, miR-29b, miR-92, miR-155, and miR-223 copies were measured by RT-PCR. Results: Large EVs were significantly bigger in the plasma collected at 10:00 versus 22:00 in both groups. There was a significant day–night increase in the quantity of 5 miRNAs in HIV− large EVs. In HIV+ART, only miR-155 daily variation has been observed in large EVs. Finally, EV-miRNA content permits to distinguish HIV− to HIV+ART in multivariate analysis. Conclusion: These results point that plasma EV amount and microRNA contents are under daily variation in HIV− people. This new dynamic measure is disrupted in PLWH despite viral-suppressive ART. This study highlights a significant difference concerning EV abundance and their content measured at 22:00 between both groups. Therefore, the time of blood collection must be considered in the future for the EV as biomarkers.

Highlights

During the last decade, extracellular vesicles (EVs) have been identified in many biological fluids and have gained importance as cell-to-cell communicators [1,2]
Large and small EVs were purified from proteinase K pretreated plasma, and their size was evaluated by dynamic light scattering (DLS) (Figure 1A)
Small EVs size at 10:00 was respectively correlated with Human Immunodeficiency Virus (HIV) infection duration (r = 0.75, p = 0.0154; Figure 1F) and ART duration (r = 0.85, p = 0.0029; Figure 1G). These results show that only large EV was subject to circadian variation in both groups and HIV infection does not disturb this physiological state

Summary

Introduction

Extracellular vesicles (EVs) have been identified in many biological fluids and have gained importance as cell-to-cell communicators [1,2]. Emerging roles for therapeutic opportunities regardless of multifaceted biological functions are observed [9] They have been reported to carry cellular components that have functional effects on neighboring or distant cells, including mRNA and microRNA, other noncoding RNA, cytoplasmic and membrane proteins, and lipids [7]. We investigated daily variations of large and small EVs, in terms of abundance and microRNA contents in people living with HIV (PLWH) receiving antiretroviral therapy (HIV+ART) and uninfected controls (HIV−). Conclusion: These results point that plasma EV amount and microRNA contents are under daily variation in HIV− people. This new dynamic measure is disrupted in PLWH despite viral-suppressive ART. The time of blood collection must be considered in the future for the EV as biomarkers

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Results

Discussion

Conclusion