Development of a huBLT Mouse Model to Study HCMV Latency, Reactivation, and Immune Response

Lindsey B. Crawford, Patrizia Caposio

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Immunodeficient mice engrafted with human tissues provide a robust model for the in vivo investigation of human-restricted viruses such as human cytomegalovirus (HCMV). Several humanized mouse models have been developed and improved over the last 30 years. Here, we describe a protocol for the transplant of human hematopoietic stem cells with autologous fetal liver and thymic tissues into NOD.Cg-PrkdcscidIL2rγtm1Wjl mice to create a humanized bone marrow–liver–thymus model (huBLT) that can be infected with HCMV. The presence of human thymus allows the development of a functional human immune system, including HLA-restricted human T-cells and B-cells. Indeed, following infection, huBLT mice generate virus-specific CD4+ and CD8+ T-cell responses. Additionally, both HCMV-specific IgM and IgG B-cell responses can be detected. This huBLT model provides the first animal model to explore the adaptive human immune response to HCMV infection.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages343-363
Number of pages21
DOIs
StatePublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2244
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • B-cell response
  • Hematopoietic progenitor cells
  • huBLT
  • Human Cytomegalovirus
  • Humanized mice
  • T-cell response
  • Thymus

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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