Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses

Humanized mouse models are used as comprehensive small-animal models of EBV infection. Previously, infectious doses of EBV used in vivo have been determined mainly on the basis of TD<sub>50</sub> (50% transforming dose), which is a time-consuming process. Here, we determined infectious d...

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Autores principales:	Haiwen Chen, Ling Zhong, Wanlin Zhang, Shanshan Zhang, Junping Hong, Xiang Zhou, Xinyu Zhang, Qisheng Feng, Yixin Chen, Yi-Xin Zeng, Miao Xu, Claude Krummenacher, Xiao Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	EBV infection green Raji units humanized mouse models CD8<sup>+</sup> T cells CD19<sup>+</sup> B cells Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/675a241fb71c4138aebb8afb957eef01
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spelling	oai:doaj.org-article:675a241fb71c4138aebb8afb957eef012021-11-25T19:13:09ZDose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses10.3390/v131121841999-4915https://doaj.org/article/675a241fb71c4138aebb8afb957eef012021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2184https://doaj.org/toc/1999-4915Humanized mouse models are used as comprehensive small-animal models of EBV infection. Previously, infectious doses of EBV used in vivo have been determined mainly on the basis of TD<sub>50</sub> (50% transforming dose), which is a time-consuming process. Here, we determined infectious doses of Akata-EBV-GFP using green Raji units (GRUs), and characterized dose-dependent effects in humanized mice. We defined two outcomes in vivo, including an infection model and a lymphoma model, following inoculation with low or high doses of Akata-EBV-GFP, respectively. Inoculation with a low dose induced primary B cells to become lymphoblastoid cell lines in vitro, and caused latent infection in humanized mice. In contrast, a high dose of Akata-EBV-GFP resulted in primary B cells death in vitro, and fatal B cell lymphomas in vivo. Following infection with high doses, the frequency of CD19<sup>+</sup> B cells decreased, whereas the percentage of CD8<sup>+</sup> T cells increased in peripheral blood and the spleen. At such doses, a small part of activated CD8<sup>+</sup> T cells was EBV-specific CD8<sup>+</sup> T cells. Thus, GRUs quantitation of Akata-EBV-GFP is an effective way to quantify infectious doses to study pathologies, immune response, and to assess (in vivo) the neutralizing activity of antibodies raised by immunization against EBV.Haiwen ChenLing ZhongWanlin ZhangShanshan ZhangJunping HongXiang ZhouXinyu ZhangQisheng FengYixin ChenYi-Xin ZengMiao XuClaude KrummenacherXiao ZhangMDPI AGarticleEBV infectiongreen Raji unitshumanized mouse modelsCD8<sup>+</sup> T cellsCD19<sup>+</sup> B cellsMicrobiologyQR1-502ENViruses, Vol 13, Iss 2184, p 2184 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EBV infection green Raji units humanized mouse models CD8<sup>+</sup> T cells CD19<sup>+</sup> B cells Microbiology QR1-502
spellingShingle	EBV infection green Raji units humanized mouse models CD8<sup>+</sup> T cells CD19<sup>+</sup> B cells Microbiology QR1-502 Haiwen Chen Ling Zhong Wanlin Zhang Shanshan Zhang Junping Hong Xiang Zhou Xinyu Zhang Qisheng Feng Yixin Chen Yi-Xin Zeng Miao Xu Claude Krummenacher Xiao Zhang Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses
description	Humanized mouse models are used as comprehensive small-animal models of EBV infection. Previously, infectious doses of EBV used in vivo have been determined mainly on the basis of TD<sub>50</sub> (50% transforming dose), which is a time-consuming process. Here, we determined infectious doses of Akata-EBV-GFP using green Raji units (GRUs), and characterized dose-dependent effects in humanized mice. We defined two outcomes in vivo, including an infection model and a lymphoma model, following inoculation with low or high doses of Akata-EBV-GFP, respectively. Inoculation with a low dose induced primary B cells to become lymphoblastoid cell lines in vitro, and caused latent infection in humanized mice. In contrast, a high dose of Akata-EBV-GFP resulted in primary B cells death in vitro, and fatal B cell lymphomas in vivo. Following infection with high doses, the frequency of CD19<sup>+</sup> B cells decreased, whereas the percentage of CD8<sup>+</sup> T cells increased in peripheral blood and the spleen. At such doses, a small part of activated CD8<sup>+</sup> T cells was EBV-specific CD8<sup>+</sup> T cells. Thus, GRUs quantitation of Akata-EBV-GFP is an effective way to quantify infectious doses to study pathologies, immune response, and to assess (in vivo) the neutralizing activity of antibodies raised by immunization against EBV.
format	article
author	Haiwen Chen Ling Zhong Wanlin Zhang Shanshan Zhang Junping Hong Xiang Zhou Xinyu Zhang Qisheng Feng Yixin Chen Yi-Xin Zeng Miao Xu Claude Krummenacher Xiao Zhang
author_facet	Haiwen Chen Ling Zhong Wanlin Zhang Shanshan Zhang Junping Hong Xiang Zhou Xinyu Zhang Qisheng Feng Yixin Chen Yi-Xin Zeng Miao Xu Claude Krummenacher Xiao Zhang
author_sort	Haiwen Chen
title	Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses
title_short	Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses
title_full	Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses
title_fullStr	Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses
title_full_unstemmed	Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses
title_sort	dose-dependent outcome of ebv infection of humanized mice based on green raji unit (gru) doses
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/675a241fb71c4138aebb8afb957eef01
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Dose-Dependent Outcome of EBV Infection of Humanized Mice Based on Green Raji Unit (GRU) Doses

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