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  • Oral presentation
  • Open Access

Disseminated and sustained HIV-infection in CD34+ cord blood cell transplanted Rag2-/-gc-/- mice

  • 1,
  • 2,
  • 1,
  • 3,
  • 1,
  • 1,
  • 1,
  • 4,
  • 5,
  • 1,
  • 1,
  • 2 and
  • 1
Retrovirology20063 (Suppl 1) :S31

https://doi.org/10.1186/1742-4690-3-S1-S31

  • Published:

Keywords

  • Cord Blood
  • Lymphoid Organ
  • Human CD34
  • Cell Depletion
  • Initial Rise

Background

We evaluated a novel mouse model that is based on the transplantation of human cord blood CD34+cells into immunodeficient Rag2-/-gc-/- newborn mice for studying HIV.

Results

Reconstituted mice (CD45+ cell engraftment: 29 ± 18%) were permissive to HIV with up to 2 × 106 copies/ml 2–6 weeks after infection. Thereafter, viremia stabilized at lower levels for up to 4 months. A marked CD4+ cell depletion occurred in all mice infected with X4- strains simultaneously with the initial rise of plasma HIV RNA while this was not the case in R5-infected mice. Spleens and lymph nodes of mice infected with either R5- or X4- strains contained p24+ cells. In thymi, however, p24+ cells were detected rather exclusively following infection with X4- strain, consistent with the expression of CXCR4 but not CCR5 on human CD4+ thymocytes. Similarly as in humans, HIV-infected macrophages were only occasionally found.

Conclusion

Rag2-/-gc-/- mice transplanted with human CD34+ cells develop long-term, high-titer, and lymphoid organ disseminated infection irrespective of co-receptor selectivity of HIV strain, closely resembling HIV infection in man. In particular, by using HIV strains with distinct co-receptor selectivity, we clearly illustrate the higher cytopathic potential of X4- strains as compared to R5- strains. This straightforward to generate and cost-effective in vivo model should be valuable to study virus-induced pathology, and to rapidly evaluate new approaches aiming to prevent or treat HIV infection.

Authors’ Affiliations

(1)
University Hospital of Zurich, Zurich, Switzerland
(2)
Institute for Research in Biomedicine, Bellinzona, Switzerland
(3)
Institute for Pathology, Locarno, Switzerland
(4)
University of Berne, Berne, Switzerland
(5)
Swiss Federal Institute of Technology, Zurich, Switzerland

Copyright

© Baenziger et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.

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