Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2-/- c-/- Mice

Centere for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Journal of Virology (Impact Factor: 4.44). 04/2007; 81(6):2700-12. DOI: 10.1128/JVI.02010-06
Source: PubMed


The specificity of human immunodeficiency virus type 1 (HIV-1) for human cells precludes virus infection in most mammalian
species and limits the utility of small animal models for studies of disease pathogenesis, therapy, and vaccine development.
One way to overcome this limitation is by human cell xenotransplantation in immune-deficient mice. However, this has proved
inadequate, as engraftment of human immune cells is limited (both functionally and quantitatively) following transplantation
of mature human lymphocytes or fetal thymus/liver. To this end, a human immune system was generated from umbilical cord blood-derived
CD34+ hematopoietic stem cells in BALB/c-Rag2−/−γc−/− mice. Intrapartum busulfan administration followed by irradiation of newborn pups resulted in uniform engraftment characterized
by human T-cell development in thymus, B-cell maturation in bone marrow, lymph node development, immunoglobulin M (IgM)/IgG
production, and humoral immune responses following ActHIB vaccination. Infection of reconstituted mice by CCR5-coreceptor
utilizing HIV-1ADA and subtype C 1157 viral strains elicited productive viral replication and lymphadenopathy in a dose-dependent fashion. We
conclude that humanized BALB/c-Rag2−/−γc−/− mice represent a unique and valuable resource for HIV-1 pathobiology studies.

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    • "The University of Nebraska Medical Center Institutional Review Board approved human fetal tissue usage. CD34+ hematopoietic stem cells (HSC) were isolated from human fetal liver by immune selection (Miltenyl Biotec Inc., Auburn, CA) then transplanted into NSG mice at birth (Gorantla et al., 2007). At 22 weeks of age mice were infected with a 10 4 tissue culture infective dose 50 0166-3542/Ó 2015 Elsevier B.V. All rights reserved. "
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    • "We consequently investigated whether PD-1 blockade could also increase the titer of HIV-specific antibodies in chronically HIV-infected BLT mice. Several prior studies of HIV infection in other humanized mouse models found little or no production of HIV-specific IgM or IgG antibodies post-infection [45], [46], [47]. In earlier work with the BLT mouse model, we showed that these mice can generate antibodies against a number of HIV antigens after infection, but did not analyze the isotypes of the antibodies produced [25]. "
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    • ") CD4 depletion / Cellular RG ( Berges et al . , 2006 ; An et al . , 2007 ; Zhang et al . , 2007 ; Baenziger et al . , 2006 ; Berges et al . , 2010 ) Cellular ( CD8 depletion ) NSG ( Gorantla et al . , 2010b ) Cellular NOK ( HLA ) ( Sato et al . , 2012 ) Humoral RG ( Gorantla et al . , 2007 ) Humoral NOG ( Watanabe et al . , 2007 ) Cellular / Humoral NSG ( Singh et al . , 2012 ) Cellular / Humoral NSG - BLT , NOD / SCID - BLT ( Brainard et al . , 2009 ) Cellular / Humoral NOG ( Sato et al . , 2010 ) Humoral NSG ( Chang et al . , 2012 ) Nef and replication BLT ( Zou et al . , 2012 ) Vpu and replication NOG ( Sato et al . , "
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