title: Superior human leukocyte reconstitution and susceptibility to vaginal HIV transmission in humanized NOD-scid IL-2Rγ(-/-) (NSG) BLT mice.
abstract: Humanized Bone marrow/Liver/Thymus (BLT) mice recapitulate the mucosal transmission of HIV, permitting study of early events in HIV pathogenesis and evaluation of preexposure prophylaxis methods to inhibit HIV transmission. Human hematopoiesis is reconstituted in NOD-scid mice by implantation of human fetal liver and thymus tissue to generate human T cells plus intravenous injection of autologous liver-derived CD34(+) hematopoietic stem cells to engraft the mouse bone marrow. In side-by-side comparisons, we show that NOD-scid mice homozygous for a deletion of the IL-2Rγ-chain (NOD-scid IL-2Rγ(-/-)) are far superior to NOD-scid mice in both their peripheral blood reconstitution with multiple classes of human leukocytes (e.g., a mean of 182 versus 14 CD4(+) T cells per μl 12 weeks after CD34(+) injection) and their susceptibility to intravaginal HIV exposure (84% versus 11% viremic mice at 4 weeks). These results should speed efforts to obtain preclinical animal efficacy data for new HIV drugs and microbicides.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA 94110, USA. cheryl.stoddart@ucsf.edu
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Stoddart
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Maidji
authors.forename: Sofiya A
authors.initials: SA
authors.lastname: Galkina
authors.forename: Galina
authors.initials: G
authors.lastname: Kosikova
authors.forename: Jose M
authors.initials: JM
authors.lastname: Rivera
authors.forename: Mary E
authors.initials: ME
authors.lastname: Moreno
authors.forename: Barbara
authors.initials: B
authors.lastname: Sloan
authors.forename: Pheroze
authors.initials: P
authors.lastname: Joshi
authors.forename: Brian R
authors.initials: BR
authors.lastname: Long
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D004198:Disease Susceptibility; D005260:Female; D006678:HIV / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000635:transmission*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D014183:Transplantation, Heterologous; D014621:Vagina
chemical_list: D018952:Antigens, CD34; D053631:Interleukin Receptor Common gamma Subunit