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Gammaherpesvirus Infection of Human Neuronal Cells
Gammaherpesviruses human herpesvirus 4 (HHV4) and HHV8 are two prominent members of the herpesvirus family associated with a number of human cancers. HHV4, also known as Epstein-Barr virus (EBV), a ubiquitous gammaherpesvirus prevalent in 90 to 95% of the human population, is clinically associated w...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669387/ https://www.ncbi.nlm.nih.gov/pubmed/26628726 http://dx.doi.org/10.1128/mBio.01844-15 |
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author | Jha, Hem Chandra Mehta, Devan Lu, Jie El-Naccache, Darine Shukla, Sanket K. Kovacsics, Colleen Kolson, Dennis Robertson, Erle S. |
author_facet | Jha, Hem Chandra Mehta, Devan Lu, Jie El-Naccache, Darine Shukla, Sanket K. Kovacsics, Colleen Kolson, Dennis Robertson, Erle S. |
author_sort | Jha, Hem Chandra |
collection | PubMed |
description | Gammaherpesviruses human herpesvirus 4 (HHV4) and HHV8 are two prominent members of the herpesvirus family associated with a number of human cancers. HHV4, also known as Epstein-Barr virus (EBV), a ubiquitous gammaherpesvirus prevalent in 90 to 95% of the human population, is clinically associated with various neurological diseases such as primary central nervous system lymphoma, multiple sclerosis, Alzheimer’s disease, cerebellar ataxia, and encephalitis. However, the possibility that EBV and Kaposi’s sarcoma-associated herpesvirus (KSHV) can directly infect neurons has been largely overlooked. This study has, for the first time, characterized EBV infection in neural cell backgrounds by using the Sh-Sy5y neuroblastoma cell line, teratocarcinoma Ntera2 neurons, and primary human fetal neurons. Furthermore, we also demonstrated KSHV infection of neural Sh-Sy5y cells. These neuronal cells were infected with green fluorescent protein-expressing recombinant EBV or KSHV. Microscopy, genetic analysis, immunofluorescence, and Western blot analyses for specific viral antigens supported and validated the infection of these cells by EBV and KSHV and showed that the infection was efficient and productive. Progeny virus produced from infected neuronal cells efficiently infected fresh neuronal cells, as well as peripheral blood mononuclear cells. Furthermore, acyclovir was effective at inhibiting the production of virus from neuronal cells similar to lymphoblastoid cell lines; this suggests active lytic replication in infected neurons in vitro. These studies represent a potentially new in vitro model of EBV- and KSHV-associated neuronal disease development and pathogenesis. |
format | Online Article Text |
id | pubmed-4669387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-46693872015-12-10 Gammaherpesvirus Infection of Human Neuronal Cells Jha, Hem Chandra Mehta, Devan Lu, Jie El-Naccache, Darine Shukla, Sanket K. Kovacsics, Colleen Kolson, Dennis Robertson, Erle S. mBio Research Article Gammaherpesviruses human herpesvirus 4 (HHV4) and HHV8 are two prominent members of the herpesvirus family associated with a number of human cancers. HHV4, also known as Epstein-Barr virus (EBV), a ubiquitous gammaherpesvirus prevalent in 90 to 95% of the human population, is clinically associated with various neurological diseases such as primary central nervous system lymphoma, multiple sclerosis, Alzheimer’s disease, cerebellar ataxia, and encephalitis. However, the possibility that EBV and Kaposi’s sarcoma-associated herpesvirus (KSHV) can directly infect neurons has been largely overlooked. This study has, for the first time, characterized EBV infection in neural cell backgrounds by using the Sh-Sy5y neuroblastoma cell line, teratocarcinoma Ntera2 neurons, and primary human fetal neurons. Furthermore, we also demonstrated KSHV infection of neural Sh-Sy5y cells. These neuronal cells were infected with green fluorescent protein-expressing recombinant EBV or KSHV. Microscopy, genetic analysis, immunofluorescence, and Western blot analyses for specific viral antigens supported and validated the infection of these cells by EBV and KSHV and showed that the infection was efficient and productive. Progeny virus produced from infected neuronal cells efficiently infected fresh neuronal cells, as well as peripheral blood mononuclear cells. Furthermore, acyclovir was effective at inhibiting the production of virus from neuronal cells similar to lymphoblastoid cell lines; this suggests active lytic replication in infected neurons in vitro. These studies represent a potentially new in vitro model of EBV- and KSHV-associated neuronal disease development and pathogenesis. American Society of Microbiology 2015-12-01 /pmc/articles/PMC4669387/ /pubmed/26628726 http://dx.doi.org/10.1128/mBio.01844-15 Text en Copyright © 2015 Jha et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jha, Hem Chandra Mehta, Devan Lu, Jie El-Naccache, Darine Shukla, Sanket K. Kovacsics, Colleen Kolson, Dennis Robertson, Erle S. Gammaherpesvirus Infection of Human Neuronal Cells |
title | Gammaherpesvirus Infection of Human Neuronal Cells |
title_full | Gammaherpesvirus Infection of Human Neuronal Cells |
title_fullStr | Gammaherpesvirus Infection of Human Neuronal Cells |
title_full_unstemmed | Gammaherpesvirus Infection of Human Neuronal Cells |
title_short | Gammaherpesvirus Infection of Human Neuronal Cells |
title_sort | gammaherpesvirus infection of human neuronal cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669387/ https://www.ncbi.nlm.nih.gov/pubmed/26628726 http://dx.doi.org/10.1128/mBio.01844-15 |
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