Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells

Catherine Demarino, Michelle L. Pleet, Maria Cowen, Robert A. Barclay, Yao Akpamagbo, James Erickson, Nicaise Ndembe, Manhattan Charurat, Jibreel Jumare, Sunday Bwala, Peter Alabi, Max Hogan, Archana Gupta, Nicole Noren Hooten, Michele K. Evans, Benjamin Lepene, Weidong Zhou, Massimo Caputi, Fabio Romerio, Walter RoyalNazira El-Hage, Lance A. Liotta, Fatah Kashanchi

Research output: Contribution to journalArticlepeer-review

Abstract

To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids. We determined possible mechanisms involved in the selective packaging of HIV-1 RNA into EVs, specifically an increase in EV-associated hnRNP A2/B1. More recent experiments have shown that several other FDA-approved drugs have the ability to alter the content of exosomes released from HIV-1-infected cells. These findings on cART-altered EV content can also be applied to general viral inhibitors (interferons) which are used to treat other chronic infections. Additionally, we describe unique mechanisms of ESCRT pathway manipulation by antivirals, specifically the targeting of VPS4. Collectively, these data imply that, despite antiretroviral therapy, EVs containing viral products are continually released and may cause neurocognitive and immunological dysfunction.

Original languageEnglish (US)
Article number7653
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • General

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