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

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2008_Hofer_ J. Virol_08.pdf
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2008
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Hofer, Ursula
Baenziger, Stefan
Heikenwalder, Mathias
Schlaepfer, Erika
Gehre, Nadine
Regenass, Stephan
Speck, Roberto
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Journal of Virology. 2008, 82(24), pp. 12145-12153. ISSN 0022-538X. eISSN 1098-5514. Available under: doi: 10.1128/JVI.01105-08
Zusammenfassung

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-1 , 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.

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570 Biowissenschaften, Biologie
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ISO 690HOFER, Ursula, Stefan BAENZIGER, Mathias HEIKENWALDER, Erika SCHLAEPFER, Nadine GEHRE, Stephan REGENASS, Thomas BRUNNER, Roberto SPECK, 2008. 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. In: Journal of Virology. 2008, 82(24), pp. 12145-12153. ISSN 0022-538X. eISSN 1098-5514. Available under: doi: 10.1128/JVI.01105-08
BibTex
@article{Hofer2008-12gamma-14264,
  year={2008},
  doi={10.1128/JVI.01105-08},
  title={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},
  number={24},
  volume={82},
  issn={0022-538X},
  journal={Journal of Virology},
  pages={12145--12153},
  author={Hofer, Ursula and Baenziger, Stefan and Heikenwalder, Mathias and Schlaepfer, Erika and Gehre, Nadine and Regenass, Stephan and Brunner, Thomas and Speck, Roberto}
}
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