Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1

Zhifeng Sun, Paul W. Denton, Jacob D. Estes, Florence A. Othieno, Bangdong L. Wei, Anja K. Wege, Michael W. Melkus, Angela Padgett-Thomas, Mary Zupancic, Ashley T. Haase, J. Victor Garcia

Research output: Contribution to journalArticle

192 Scopus citations

Abstract

Intrarectal infection between men who have sex with men represents a predominant form of human immunodeficiency virus (HIV) transmission in developed countries. Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocytes generated in situ from hematopoietic stem cells reconstitute the gastrointestinal tract of humanized mice with human CD4+ T cells rendering them susceptible to intrarectal HIV transmission. HIV infection after a single intrarectal inoculation results in systemic infection with depletion of CD4+ T cells in gut-associated lymphoid tissue and other pathologic sequela that closely mimics those observed in HIV infected humans. This novel model provides the basis for the development and evaluation of novel approaches aimed at immune reconstitution of human gut-associated lymphoid tissue and for the development, testing, and implementation of microbicides to prevent intrarectal HIV-1 transmission. JEM

Original languageEnglish (US)
Pages (from-to)705-714
Number of pages10
JournalJournal of Experimental Medicine
Volume204
Issue number4
DOIs
StatePublished - Apr 16 2007

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Sun, Z., Denton, P. W., Estes, J. D., Othieno, F. A., Wei, B. L., Wege, A. K., Melkus, M. W., Padgett-Thomas, A., Zupancic, M., Haase, A. T., & Garcia, J. V. (2007). Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. Journal of Experimental Medicine, 204(4), 705-714. https://doi.org/10.1084/jem.20062411