Viruses (Oct 2021)

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

  • 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

DOI
https://doi.org/10.3390/v13112184
Journal volume & issue
Vol. 13, no. 11
p. 2184

Abstract

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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.

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