Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control

Poveda, Eva; Tabernilla, Andrés; Fitzgerald, Wendy; Salgado‐Barreira, Ángel; Grandal, Marta; Pérez, Alexandre; Mariño, Ana; Álvarez, Hortensia; Valcarce, Nieves; González-García, Juan; Bernardino, José I; Gutiérrez, Félix; Fujioka, Hisashi; Crespo, Manuel; Ruiz‐Mateos, Ezequiel; Margolis, Leonid; Lederman, Michael M.; Freeman, Michael L.

doi:10.1093/infdis/jiaa375

Cited by 15 publications

(15 citation statements)

References 49 publications

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“…We isolated pEVs from 1-4 ml of EDTA plasma samples by precipitation or by using affinity spin columns ( 24 ). Although studies have shown that HIV patients have higher numbers of pEVs than HCs ( 11 , 25 , 26 ) we did not observe any difference in the concentrations of EV protein and numbers obtained from the plasma of HCs, HIV ART-naïve and HIV patients on ART ( Figures 1A, B ) . pEV yields ranged from 1 x 10 9 – 4 x10 9 pEVs/100 µg protein ( Figure 1A ).…”

Section: Resultscontrasting

confidence: 68%

Plasma Extracellular Vesicles Enhance HIV-1 Infection of Activated CD4+ T Cells and Promote the Activation of Latently Infected J-Lat10.6 Cells via miR-139-5p Transfer

Okoye

Oyegbami

et al. 2021

Front. Immunol.

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HIV latency is a challenge to the success of antiretroviral therapy (ART). Hence patients may benefit from interventions that efficiently reactivate the latent virus to be eliminated by ARTs. Here we show that plasma extracellular vesicles (pEVs) can enhance HIV infection of activated CD4+ T cells and reactivate the virus in latently infected J-Lat 10.6 cells. Evaluation of the extravesicular miRNA cargo by a PCR array revealed that pEVs from HIV patients express miR-139-5p. Furthermore, we found that increased levels of miR-139-5p in J-Lat 10.6 cells incubated with pEVs corresponded with reduced expression of the transcription factor, FOXO1. pEV treatment also corresponded with increased miR-139-5p expression in stimulated PD1+ Jurkat cells, but with concomitant upregulation of FOXO1, Fos, Jun, PD-1 and PD-L1. However, J-Lat 10.6 cells incubated with miR-139-5p inhibitor-transfected pEVs from HIV ART-naïve and on-ART patients expressed reduced levels of miR-139-5p than cells treated with pEVs from healthy controls (HC). Collectively, our results indicate that pEV miR-139-5p belongs to a network of miRNAs that can promote cell activation, including latent HIV-infected cells by regulating the expression of FOXO1 and the PD1/PD-L1 promoters, Fos and Jun.

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Section: Resultscontrasting

confidence: 68%

Plasma Extracellular Vesicles Enhance HIV-1 Infection of Activated CD4+ T Cells and Promote the Activation of Latently Infected J-Lat10.6 Cells via miR-139-5p Transfer

Okoye

Oyegbami

et al. 2021

Front. Immunol.

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“…MVs released by virus-infected cells may serve as a biomarker for virus infection. For example, during HIV infection, platelets abundantly release MVs containing mitochondria, which are different from those of healthy cells; suggesting biomarker for HIV infection [59]. During virus infection, the shedding of MVs containing viral proteins and glycoproteins, can make surrounding cells susceptible to infection and reduce immune responses [60,61].…”

Section: Extracellular Vesicles and Virusmentioning

confidence: 99%

The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application

et al. 2021

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Eukaryotic cells produce extracellular vesicles (EVs) mediating intercellular communication. These vesicles encompass many bio-molecules such as proteins, nucleic acids, and lipids that are transported between cells and regulate pathophysiological actions in the recipient cell. Exosomes originate from multivesicular bodies inside cells and microvesicles shed from the plasma membrane and participate in various pathological conditions. Retroviruses such as Human Immunodeficiency Virus -type 1 (HIV-1) and Human T-cell leukemia virus (HTLV)-1 engage exosomes for spreading and infection. Exosomes from virus-infected cells transfer viral components such as miRNAs and proteins that promote infection and inflammation. Additionally, these exosomes deliver virus receptors to target cells that make them susceptible to virus entry. HIV-1 infected cells release exosomes that contribute to the pathogenesis including neurological disorders and malignancy. Exosomes can also potentially carry out as a modern approach for the development of HIV-1 and HTLV-1 vaccines. Furthermore, as exosomes are present in most biological fluids, they hold the supreme capacity for clinical usage in the early diagnosis and prognosis of viral infection and associated diseases. Our current knowledge of exosomes' role from virus-infected cells may provide an avenue for efficient retroviruses associated with disease prevention. However, the exact mechanism involved in retroviruses infection/ inflammation remains elusive and related exosomes research will shed light on the mechanisms of pathogenesis.

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“…HIV-1 Tat binds to the chemokine receptor CCR3 and b integrin on platelets, leading to the release of PMVs [26,83]. Platelet derived extracellular vesicles can be used as inflammation markers and immune activation markers in HIV infection and are related to procoagulant activity [84][85][86][87].…”

Section: The Role Of Pmvs In Viral Infectionsmentioning

confidence: 99%

Platelet-Released Factors: Their Role in Viral Disease and Applications for Extracellular Vesicle (EV) Therapy

Ostermeier

Soriano-Sarabia

Maggirwar

2022

IJMS

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Platelets, which are small anuclear cell fragments, play important roles in thrombosis and hemostasis, but also actively release factors that can both suppress and induce viral infections. Platelet-released factors include sCD40L, microvesicles (MVs), and alpha granules that have the capacity to exert either pro-inflammatory or anti-inflammatory effects depending on the virus. These factors are prime targets for use in extracellular vesicle (EV)-based therapy due to their ability to reduce viral infections and exert anti-inflammatory effects. While there are some studies regarding platelet microvesicle-based (PMV-based) therapy, there is still much to learn about PMVs before such therapy can be used. This review provides the background necessary to understand the roles of platelet-released factors, how these factors might be useful in PMV-based therapy, and a critical discussion of current knowledge of platelets and their role in viral diseases.

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Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control

Cited by 15 publications

References 49 publications

Plasma Extracellular Vesicles Enhance HIV-1 Infection of Activated CD4+ T Cells and Promote the Activation of Latently Infected J-Lat10.6 Cells via miR-139-5p Transfer

Plasma Extracellular Vesicles Enhance HIV-1 Infection of Activated CD4+ T Cells and Promote the Activation of Latently Infected J-Lat10.6 Cells via miR-139-5p Transfer

The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application

Platelet-Released Factors: Their Role in Viral Disease and Applications for Extracellular Vesicle (EV) Therapy

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