Sequences within RNA coding for HIV-1 Gag p17 are efficiently targeted to exosomes

Columba-Cabezas, Sandra; Federico, Maurizio

doi:10.1111/cmi.12046

Cited by 52 publications

(43 citation statements)

References 38 publications

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“…HIV-1-infected cells release exosomes associating with viral proteins (5-7) and RNA (27,28). Recently, it has been reported that exosomes from cells expressing Nef upload activated ADAM17 and induce release of TNF-␣ from unstimulated PBMCs (8).…”

Section: Discussionmentioning

confidence: 99%

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 ⁺ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

Arenaccio

Chiozzini

Columba-Cabezas

et al. 2014

J Virol

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150

143

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Resting CD4؉ T lymphocytes resist human immunodeficiency virus (HIV) infection. Here, we provide evidence that exosomes from HIV-1-infected cells render resting human primary CD4 ؉ T lymphocytes permissive to HIV-1 replication. These results were obtained with transwell cocultures of HIV-1-infected cells with quiescent CD4؉ T lymphocytes in the presence of inhibitors of exosome release and were confirmed using exosomes purified from supernatants of HIV-1-infected primary CD4؉ T lymphocytes. We found that the expression of HIV-1 Nef in exosome-producing cells is both necessary and sufficient for cell activation as well as HIV-1 replication in target CD4 ؉ T lymphocytes. We also identified a Nef domain important for the effects we observed, i.e., the 62 EEEE 65 acidic cluster domain. In addition, we observed that ADAM17, i.e., a disintegrin and metalloprotease converting pro-tumor necrosis factor alpha (TNF- ␣

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Section: Discussionmentioning

confidence: 99%

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 ⁺ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

Arenaccio

Chiozzini

Columba-Cabezas

et al. 2014

J Virol

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143

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“…Various HIV-1 RNAs and proteins have been detected in EVs, and effects have been imputed to some of these (8,(46)(47)(48)(49). In one report, several unspliced HIV RNA sequences were found in association with exosomes, consistent with full-length genome incorporation (46). Spliced RNAs were not detected.…”

Section: Do Other Enveloped Viruses Shuttle Genomes In Evs?mentioning

confidence: 99%

“…In another study, short HIV-1 transactivation response (TAR) element transcripts were found in exosomes released from infected cells, along with smaller RNAs processed from the TAR element (8). However, retroviral RNA conveyed in exosomes has not been found to be infectious (8,46). Similarly, exosomes from human T-lymphotropic virus type 1 (HTLV-1)-infected cells have not been found to be infectious (50).…”

Section: Do Other Enveloped Viruses Shuttle Genomes In Evs?mentioning

confidence: 99%

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Dongen

Masoumi

Witwer

et al. 2016

Microbiol Mol Biol Rev

226

193

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SUMMARYExtracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cellsin vivoand how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors.

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“…With regard to viral infection, exosomes aid in the transfer of hepatitis C virus viral RNA from infected to uninfected plasmacytoid dendritic cells, inducing the production of type I IFN (48). Furthermore, HIV-1 Gag and p17 are incorporated into exosomes released from these infected cells (49). Regarding exosome-mediated transfer of miRNA, exosomes have been shown to deliver functional miRNA from infected donor cells to uninfected recipient cells during infection by the oncogenic Epstein-Barr virus (32).…”

mentioning

confidence: 99%

Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein

Jaworski

Narayanan

Duyne

et al. 2014

Journal of Biological Chemistry

143

180

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Background: Extracellular exosomes contain various functional elements. Results: Exosomal Tax protein causes phenotypic changes in uninfected cells. Conclusion: Exosomes may play critical roles in extracellular delivery of oncogenic material derived from HTLV-1-infected cells. Significance: Exosomal delivery of Tax and other putative oncogenic components produced during HTLV-1 infection potentially contributes to pathogenesis of adult T-cell leukemia, myelopathy, or tropical spastic paraparesis.

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Sequences within RNA coding for HIV-1 Gag p17 are efficiently targeted to exosomes

Cited by 52 publications

References 38 publications

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 ⁺ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 ⁺ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein

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Sequences within RNA coding for HIV-1 Gag p17 are efficiently targeted to exosomes

Cited by 52 publications

References 38 publications

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 + T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 + T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein

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Product

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Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 ⁺ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism

Exosomes from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Cells License Quiescent CD4 ⁺ T Lymphocytes To Replicate HIV-1 through a Nef- and ADAM17-Dependent Mechanism