Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread
Abstract Background The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highl...
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BMC
2021-02-01
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Series: | Retrovirology |
Online Access: | https://doi.org/10.1186/s12977-021-00550-8 |
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doaj-4364e98badb6462b9f29686cdbb50650 |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniel O. Pinto Sarah Al Sharif Gifty Mensah Maria Cowen Pooja Khatkar James Erickson Heather Branscome Thomas Lattanze Catherine DeMarino Farhang Alem Ruben Magni Weidong Zhou Sandrine Alais Hélène Dutartre Nazira El-Hage Renaud Mahieux Lance A. Liotta Fatah Kashanchi |
spellingShingle |
Daniel O. Pinto Sarah Al Sharif Gifty Mensah Maria Cowen Pooja Khatkar James Erickson Heather Branscome Thomas Lattanze Catherine DeMarino Farhang Alem Ruben Magni Weidong Zhou Sandrine Alais Hélène Dutartre Nazira El-Hage Renaud Mahieux Lance A. Liotta Fatah Kashanchi Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread Retrovirology |
author_facet |
Daniel O. Pinto Sarah Al Sharif Gifty Mensah Maria Cowen Pooja Khatkar James Erickson Heather Branscome Thomas Lattanze Catherine DeMarino Farhang Alem Ruben Magni Weidong Zhou Sandrine Alais Hélène Dutartre Nazira El-Hage Renaud Mahieux Lance A. Liotta Fatah Kashanchi |
author_sort |
Daniel O. Pinto |
title |
Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread |
title_short |
Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread |
title_full |
Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread |
title_fullStr |
Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread |
title_full_unstemmed |
Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread |
title_sort |
extracellular vesicles from htlv-1 infected cells modulate target cells and viral spread |
publisher |
BMC |
series |
Retrovirology |
issn |
1742-4690 |
publishDate |
2021-02-01 |
description |
Abstract Background The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highly endemic areas in Japan, Africa, the Caribbean and South America. We have previously shown that Extracellular Vesicles (EVs) enhance HTLV-1 transmission by promoting cell–cell contact. Results Here, we separated EVs into subpopulations using differential ultracentrifugation (DUC) at speeds of 2 k (2000×g), 10 k (10,000×g), and 100 k (100,000×g) from infected cell supernatants. Proteomic analysis revealed that EVs contain the highest viral/host protein abundance in the 2 k subpopulation (2 k > 10 k > 100 k). The 2 k and 10 k populations contained viral proteins (i.e., p19 and Tax), and autophagy proteins (i.e., LC3 and p62) suggesting presence of autophagosomes as well as core histones. Interestingly, the use of 2 k EVs in an angiogenesis assay (mesenchymal stem cells + endothelial cells) caused deterioration of vascular-like-tubules. Cells commonly associated with the neurovascular unit (i.e., astrocytes, neurons, and macrophages) in the blood–brain barrier (BBB) showed that HTLV-1 EVs may induce expression of cytokines involved in migration (i.e., IL-8; 100 k > 2 k > 10 k) from astrocytes and monocyte-derived macrophages (i.e., IL-8; 2 k > 10 k). Finally, we found that EVs were able to promote cell–cell contact and viral transmission in monocytic cell-derived dendritic cell. The EVs from both 2 k and 10 k increased HTLV-1 spread in a humanized mouse model, as evidenced by an increase in proviral DNA and RNA in the Blood, Lymph Node, and Spleen. Conclusions Altogether, these data suggest that various EV subpopulations induce cytokine expression, tissue damage, and viral spread. |
url |
https://doi.org/10.1186/s12977-021-00550-8 |
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doaj-4364e98badb6462b9f29686cdbb506502021-02-23T10:35:45ZengBMCRetrovirology1742-46902021-02-0118112710.1186/s12977-021-00550-8Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spreadDaniel O. Pinto0Sarah Al Sharif1Gifty Mensah2Maria Cowen3Pooja Khatkar4James Erickson5Heather Branscome6Thomas Lattanze7Catherine DeMarino8Farhang Alem9Ruben Magni10Weidong Zhou11Sandrine Alais12Hélène Dutartre13Nazira El-Hage14Renaud Mahieux15Lance A. Liotta16Fatah Kashanchi17Laboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityCenter for Applied Proteomics and Molecular Medicine, George Mason UniversityCenter for Applied Proteomics and Molecular Medicine, George Mason UniversityInternational Center for Research in Infectiology, Retroviral Oncogenesis Laboratory, INSERM U1111-Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Fondation Pour La Recherche MédicaleInternational Center for Research in Infectiology, Retroviral Oncogenesis Laboratory, INSERM U1111-Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Fondation Pour La Recherche MédicaleDepartment of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International UniversityInternational Center for Research in Infectiology, Retroviral Oncogenesis Laboratory, INSERM U1111-Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon, Fondation Pour La Recherche MédicaleCenter for Applied Proteomics and Molecular Medicine, George Mason UniversityLaboratory of Molecular Virology, School of Systems Biology, George Mason UniversityAbstract Background The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highly endemic areas in Japan, Africa, the Caribbean and South America. We have previously shown that Extracellular Vesicles (EVs) enhance HTLV-1 transmission by promoting cell–cell contact. Results Here, we separated EVs into subpopulations using differential ultracentrifugation (DUC) at speeds of 2 k (2000×g), 10 k (10,000×g), and 100 k (100,000×g) from infected cell supernatants. Proteomic analysis revealed that EVs contain the highest viral/host protein abundance in the 2 k subpopulation (2 k > 10 k > 100 k). The 2 k and 10 k populations contained viral proteins (i.e., p19 and Tax), and autophagy proteins (i.e., LC3 and p62) suggesting presence of autophagosomes as well as core histones. Interestingly, the use of 2 k EVs in an angiogenesis assay (mesenchymal stem cells + endothelial cells) caused deterioration of vascular-like-tubules. Cells commonly associated with the neurovascular unit (i.e., astrocytes, neurons, and macrophages) in the blood–brain barrier (BBB) showed that HTLV-1 EVs may induce expression of cytokines involved in migration (i.e., IL-8; 100 k > 2 k > 10 k) from astrocytes and monocyte-derived macrophages (i.e., IL-8; 2 k > 10 k). Finally, we found that EVs were able to promote cell–cell contact and viral transmission in monocytic cell-derived dendritic cell. The EVs from both 2 k and 10 k increased HTLV-1 spread in a humanized mouse model, as evidenced by an increase in proviral DNA and RNA in the Blood, Lymph Node, and Spleen. Conclusions Altogether, these data suggest that various EV subpopulations induce cytokine expression, tissue damage, and viral spread.https://doi.org/10.1186/s12977-021-00550-8 |