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

Authors

Zhifeng Sun, University of Texas Southwestern Medical Center at Dallas
Paul W. Denton, University of Texas Southwestern Medical Center at DallasFollow
Jacob D. Estes, University of Minnesota
Florence A. Othieno, University of Texas Southwestern Medical Center at Dallas
Bangdong L. Wei, University of Texas Southwestern Medical Center at Dallas
Anja K. Wege, University of Texas Southwestern Medical Center at Dallas
Michael W. Melkus, University of Texas Southwestern Medical Center at Dallas
Angela Padgett-Thomas, University of Texas Southwestern Medical Center at Dallas
Mary Zupancic, University of Minnesota
Ashley T. Haase, University of Minnesota
J. Victor Garcia, University of Texas Southwestern Medical Center at Dallas

Author ORCID Identifier

Paul W. Denton

Document Type

Article

Publication Date

3-26-2007

Publication Title

Journal of Experimental Medicine

Volume

204

Issue

4

First Page

705

Last Page

714

Abstract

Intrarectal infection between men who have sex with men represents a predominant form of human immunodefi ciency 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.

Comments

© 2007 The Authors.

DOI: 10.1084/jem.20062411, http://jem.rupress.org/content/204/4/705

Recommended Citation

Sun, Zhifeng; Denton, Paul W.; Estes, Jacob D.; Othieno, Florence A.; Wei, Bangdong L.; Wege, Anja K.; Melkus, Michael W.; Padgett-Thomas, Angela; Zupancic, Mary; Haase, Ashley T.; and Garcia, J. Victor, "Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1" (2007). Biology Faculty Publications. 149.
https://digitalcommons.unomaha.edu/biofacpub/149