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Journal of Virology, December 2008, p. 12145-12153, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01105-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

RAG2–/–{gamma}c–/– Mice Transplanted with CD34+ Cells from Human Cord Blood Show Low Levels of Intestinal Engraftment and Are Resistant to Rectal Transmission of Human Immunodeficiency Virus{triangledown}

Ursula Hofer,1* Stefan Baenziger,1 Mathias Heikenwalder,2 Erika Schlaepfer,1 Nadine Gehre,1,3 Stephan Regenass,4 Thomas Brunner,5 and Roberto F. Speck1*

Division of Infectious Diseases and Hospital Epidemiology,1 Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland,2 Experimental Infectious Diseases and Cancer Research, Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital Zurich, Zurich, Switzerland,3 Division of Clinical Immunology, University Hospital Zurich, Zurich, Switzerland,4 Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland5

Received 26 May 2008/ Accepted 18 September 2008

Rectal transmission is one of the main routes of infection by human immunodeficiency virus type 1 (HIV-1). To efficiently study transmission mechanisms and prevention strategies, a small animal model permissive for rectal transmission of HIV is mandatory. We tested the susceptibility of RAG2–/–{gamma}c–/– mice transplanted with human cord blood hematopoietic stem cells to rectal infection with HIV. We rectally exposed these humanized mice to cell-free and cell-associated HIV. All mice remained HIV negative as assessed by plasma viral load. The same mice infected intraperitoneally showed high levels of HIV replication. In the gut-associated lymphatic tissue, we found disproportionately smaller numbers of human cells than in other lymphoid organs. This finding may explain the observed resistance to rectal transmission of HIV. To increase the numbers of local HIV target cells and the likelihood of HIV transmission, we treated mice with different proinflammatory stimuli: local application of interleukin-1β, addition of seminal plasma to the inoculum, or induction of colitis with dextran sodium sulfate. These procedures attracted some human leukocytes, but the transmission rate was still very low. The humanized mice showed low levels of human engraftment in the intestinal tract and seem to be resistant to rectal transmission of HIV, and thus they are an unsuitable model for this application.

* Corresponding author. Mailing address for Roberto F. Speck and Ursula Hofer: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. Phone for R. F. Speck: 41-44-2553775. Fax: 41-44-2553291. E-mail: roberto.speck{at}usz.ch. Phone for U. Hofer: 41-44-2559345. Fax: 41-44-2553291. E-mail: ursula.hofer{at}usz.ch

{triangledown} Published ahead of print on 8 October 2008.

Journal of Virology, December 2008, p. 12145-12153, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01105-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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