The Journal of Experimental Medicine
StemCell Technologies
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Published online March 26, 2007
doi:10.1084/jem.20062411
The Journal of Experimental Medicine, Vol. 204, No. 4, 705-714
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Sun et al.
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BRIEF DEFINITIVE REPORT

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

Zhifeng Sun1, Paul W. Denton1, Jacob D. Estes2, Florence A. Othieno1, Bangdong L. Wei1, Anja K. Wege1, Michael W. Melkus1, Angela Padgett-Thomas1, Mary Zupancic2, Ashley T. Haase2, and J. Victor Garcia1

1 Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390
2 Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455

CORRESPONDENCE J. Victor Garcia: victor.garcia{at}utsouthwestern.edu

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.

Z. Sun and P.W. Denton contributed equally to this work.


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