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Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission
Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells which carry signaling factors, proteins, and microRNAs that mediate intercellular communication. Accumulating evidence supports an important role of EVs in the progression of neurological conditions and both the spre...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265634/ https://www.ncbi.nlm.nih.gov/pubmed/34190582 http://dx.doi.org/10.1128/mSphere.00192-21 |
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author | York, Sara B. Sun, Li Cone, Allaura S. Duke, Leanne C. Cheerathodi, Mujeeb R. Meckes, David G. |
author_facet | York, Sara B. Sun, Li Cone, Allaura S. Duke, Leanne C. Cheerathodi, Mujeeb R. Meckes, David G. |
author_sort | York, Sara B. |
collection | PubMed |
description | Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells which carry signaling factors, proteins, and microRNAs that mediate intercellular communication. Accumulating evidence supports an important role of EVs in the progression of neurological conditions and both the spread and pathogenesis of infectious diseases. It has recently been demonstrated that EVs from hepatitis C virus (HCV)-infected individuals and cells contained replicative-competent viral RNA that was capable of infecting hepatocytes. Being a member of the same viral family, it is likely the Zika virus also hijacks EV pathways to package viral components and secrete vesicles that are infectious and potentially less immunogenic. As EVs have been shown to cross blood-brain and placental barriers, it is possible that Zika virus could usurp normal EV biology to gain access to the brain or developing fetus. Here, we demonstrate that Zika virus-infected cells secrete distinct EV subpopulations with specific viral protein profiles and infectious genomes. Zika virus infection resulted in the enhanced production of EVs with various sizes and densities compared to those released from noninfected cells. We also show that the EV-enriched tetraspanin CD63 regulates the release of EVs and Zika viral genomes and capsids following infection. Overall, these findings provide evidence for an alternative means of Zika virus transmission and demonstrate the role of EV biogenesis and trafficking proteins in the modulation of Zika virus infection and virion morphogenesis. IMPORTANCE Zika virus is a reemerging infectious disease that spread rapidly across the Caribbean and South America. Infection of pregnant women during the first trimester has been linked to microcephaly, a neurological condition where babies are born with smaller heads due to abnormal brain development. Babies born with microcephaly can develop convulsions and suffer disabilities as they age. Despite the significance of Zika virus, little is known about how the virus infects the fetus or causes disease. Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells that are present in all biological fluids. EVs carry signaling factors, proteins, and microRNAs that mediate intercellular communication. EVs have been shown to be a means by which some viruses can alter cellular environments and cross previously unpassable cellular barriers. Thus, gaining a greater understanding of how Zika virus affects EV cargo may aid in the development of better diagnostics, targeted therapeutics, and/or prophylactic treatments. |
format | Online Article Text |
id | pubmed-8265634 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-82656342021-07-23 Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission York, Sara B. Sun, Li Cone, Allaura S. Duke, Leanne C. Cheerathodi, Mujeeb R. Meckes, David G. mSphere Research Article Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells which carry signaling factors, proteins, and microRNAs that mediate intercellular communication. Accumulating evidence supports an important role of EVs in the progression of neurological conditions and both the spread and pathogenesis of infectious diseases. It has recently been demonstrated that EVs from hepatitis C virus (HCV)-infected individuals and cells contained replicative-competent viral RNA that was capable of infecting hepatocytes. Being a member of the same viral family, it is likely the Zika virus also hijacks EV pathways to package viral components and secrete vesicles that are infectious and potentially less immunogenic. As EVs have been shown to cross blood-brain and placental barriers, it is possible that Zika virus could usurp normal EV biology to gain access to the brain or developing fetus. Here, we demonstrate that Zika virus-infected cells secrete distinct EV subpopulations with specific viral protein profiles and infectious genomes. Zika virus infection resulted in the enhanced production of EVs with various sizes and densities compared to those released from noninfected cells. We also show that the EV-enriched tetraspanin CD63 regulates the release of EVs and Zika viral genomes and capsids following infection. Overall, these findings provide evidence for an alternative means of Zika virus transmission and demonstrate the role of EV biogenesis and trafficking proteins in the modulation of Zika virus infection and virion morphogenesis. IMPORTANCE Zika virus is a reemerging infectious disease that spread rapidly across the Caribbean and South America. Infection of pregnant women during the first trimester has been linked to microcephaly, a neurological condition where babies are born with smaller heads due to abnormal brain development. Babies born with microcephaly can develop convulsions and suffer disabilities as they age. Despite the significance of Zika virus, little is known about how the virus infects the fetus or causes disease. Extracellular vesicles (EVs) are membrane-encapsulated structures released by cells that are present in all biological fluids. EVs carry signaling factors, proteins, and microRNAs that mediate intercellular communication. EVs have been shown to be a means by which some viruses can alter cellular environments and cross previously unpassable cellular barriers. Thus, gaining a greater understanding of how Zika virus affects EV cargo may aid in the development of better diagnostics, targeted therapeutics, and/or prophylactic treatments. American Society for Microbiology 2021-06-30 /pmc/articles/PMC8265634/ /pubmed/34190582 http://dx.doi.org/10.1128/mSphere.00192-21 Text en Copyright © 2021 York et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article York, Sara B. Sun, Li Cone, Allaura S. Duke, Leanne C. Cheerathodi, Mujeeb R. Meckes, David G. Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission |
title | Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission |
title_full | Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission |
title_fullStr | Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission |
title_full_unstemmed | Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission |
title_short | Zika Virus Hijacks Extracellular Vesicle Tetraspanin Pathways for Cell-to-Cell Transmission |
title_sort | zika virus hijacks extracellular vesicle tetraspanin pathways for cell-to-cell transmission |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265634/ https://www.ncbi.nlm.nih.gov/pubmed/34190582 http://dx.doi.org/10.1128/mSphere.00192-21 |
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