Submitted July 10, 2006
Accepted November 21, 2006
HIV-1 infection and pathogenesis in a novel humanized mouse model
Liguo Zhang, Grigoriy I Kovalev, and Lishan Su*
Department of Microbiology and Immunology, The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
* Corresponding author; email: lsu{at}med.unc.edu.
The Rag2-
C double knockout (DKO) mouse lacks T, B and NK cells, and allows development of a functional human immune system with human CD34+ hematopoietic stem/progenitor cells (DKO-hu HSC). Normal human T, B, and dendritic cells are present in peripheral blood, thymus, spleen and lymph nodes. We report that both CCR5 and CXCR4 are expressed on human immature and mature T cells. DKO-hu HSC mice allow efficient HIV-1 infection with plasma high viremia. High levels of productive infection occur in the thymus, spleen and lymph nodes. Human CD4+ T cells are gradually depleted by HIV-1 in a dose-dependent manner. In addition, HIV-1 infection persists in infected DKO-hu HSC mice for at least 19 weeks, with infectious HIV-1 in lymphoid tissues. Thus, the DKO-hu HSC mouse can serve as a relevant in vivo model to investigate mechanisms of HIV-1 infection and immuno-pathogenesis as well as to develop anti-HIV-1 therapeutics.
