HIV-1 infection and pathogenesis in a novel humanized mouse model

Liguo Zhang, Grigoriy I. Kovalev, Lishan Su

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)

Abstract

The Rag2-γC double-knockout (DKO) mouse lacks T, B, and natural killer (NK) cells, and allows development of a functional human immune system with human CD34+ hematopoietic stem/progenitor cells (DKO-hu HSCs). 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 immunopathogenesis as well as to develop anti-HIV-1 therapeutics.

Original languageEnglish
Pages (from-to)2978-2981
Number of pages4
JournalBlood
Volume109
Issue number7
DOIs
Publication statusPublished - 1 Apr 2007
Externally publishedYes

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