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

Authors :
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
Source :
Viruses, Vol 13, Iss 11, p 2184 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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 TD50 (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+ B cells decreased, whereas the percentage of CD8+ T cells increased in peripheral blood and the spleen. At such doses, a small part of activated CD8+ T cells was EBV-specific CD8+ 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.

Details

Language :
English
ISSN :
19994915
Volume :
13
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.675a241fb71c4138aebb8afb957eef01
Document Type :
article
Full Text :
https://doi.org/10.3390/v13112184