Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice

Abstract The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mic...

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Autores principales: Lindsey B. Crawford, Rebecca Tempel, Daniel N. Streblow, Craig Kreklywich, Patricia Smith, Louis J. Picker, Jay A. Nelson, Patrizia Caposio
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/63f137c8af204eeab7c5949faeb8e663
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spelling oai:doaj.org-article:63f137c8af204eeab7c5949faeb8e6632021-12-02T16:08:00ZHuman Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice10.1038/s41598-017-01051-52045-2322https://doaj.org/article/63f137c8af204eeab7c5949faeb8e6632017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01051-5https://doaj.org/toc/2045-2322Abstract The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice. Following infection, huBLT mice generate human effector and central memory CD4+ and CD8+ T-cell responses reactive to peptides corresponding to both IE and pp65 proteins. Additionally, both HCMV specific IgM and IgG B-cell responses with the ability to neutralize virus were detected. These results indicate that the HCMV huBLT mouse model may provide a valuable tool to study viral latency and reactivation as well as evaluate HCMV vaccines and immune responses in the context of a functional human immune system.Lindsey B. CrawfordRebecca TempelDaniel N. StreblowCraig KreklywichPatricia SmithLouis J. PickerJay A. NelsonPatrizia CaposioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lindsey B. Crawford
Rebecca Tempel
Daniel N. Streblow
Craig Kreklywich
Patricia Smith
Louis J. Picker
Jay A. Nelson
Patrizia Caposio
Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice
description Abstract The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice. Following infection, huBLT mice generate human effector and central memory CD4+ and CD8+ T-cell responses reactive to peptides corresponding to both IE and pp65 proteins. Additionally, both HCMV specific IgM and IgG B-cell responses with the ability to neutralize virus were detected. These results indicate that the HCMV huBLT mouse model may provide a valuable tool to study viral latency and reactivation as well as evaluate HCMV vaccines and immune responses in the context of a functional human immune system.
format article
author Lindsey B. Crawford
Rebecca Tempel
Daniel N. Streblow
Craig Kreklywich
Patricia Smith
Louis J. Picker
Jay A. Nelson
Patrizia Caposio
author_facet Lindsey B. Crawford
Rebecca Tempel
Daniel N. Streblow
Craig Kreklywich
Patricia Smith
Louis J. Picker
Jay A. Nelson
Patrizia Caposio
author_sort Lindsey B. Crawford
title Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice
title_short Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice
title_full Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice
title_fullStr Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice
title_full_unstemmed Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice
title_sort human cytomegalovirus induces cellular and humoral virus-specific immune responses in humanized blt mice
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/63f137c8af204eeab7c5949faeb8e663
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