PMID- 17132723 OWN - NLM STAT- MEDLINE DCOM- 20070531 LR - 20210206 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 109 IP - 7 DP - 2007 Apr 1 TI - HIV-1 infection and pathogenesis in a novel humanized mouse model. PG - 2978-81 AB - The Rag2-gammaC 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. FAU - Zhang, Liguo AU - Zhang L AD - Department of Microbiology and Immunology, The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599-7295, USA. FAU - Kovalev, Grigoriy I AU - Kovalev GI FAU - Su, Lishan AU - Su L LA - eng GR - AI/GM 48407/AI/NIAID NIH HHS/United States GR - AI041356/AI/NIAID NIH HHS/United States GR - CA99939/CA/NCI NIH HHS/United States GR - P30 AI50410/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (DNA-Binding Proteins) RN - 0 (Rag2 protein, mouse) SB - IM MH - Animals MH - DNA-Binding Proteins/deficiency/genetics MH - Disease Models, Animal MH - HIV Infections/*etiology/*immunology/virology MH - *HIV-1/physiology MH - Humans MH - Mice MH - Mice, Knockout MH - Transplantation Chimera MH - Virus Replication PMC - PMC1852218 EDAT- 2006/11/30 09:00 MHDA- 2007/06/01 09:00 PMCR- 2008/04/01 CRDT- 2006/11/30 09:00 PHST- 2006/11/30 09:00 [pubmed] PHST- 2007/06/01 09:00 [medline] PHST- 2006/11/30 09:00 [entrez] PHST- 2008/04/01 00:00 [pmc-release] AID - S0006-4971(20)41802-6 [pii] AID - 2006/033159 [pii] AID - 10.1182/blood-2006-07-033159 [doi] PST - ppublish SO - Blood. 2007 Apr 1;109(7):2978-81. doi: 10.1182/blood-2006-07-033159.