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Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2−/−γc−/− 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: 4.65). 04/2007; 81(6):2700-12. DOI: 10.1128/JVI.02010-06
Source: PubMed

ABSTRACT 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(-/-)gamma(c)(-/-) 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-1(ADA) and subtype C 1157 viral strains elicited productive viral replication and lymphadenopathy in a dose-dependent fashion. We conclude that humanized BALB/c-Rag2(-/-)gamma(c)(-/-) 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 http://dx.doi.org/10.1016/j.antiviral.2015.05.009 0166-3542/Ó 2015 Elsevier B.V. All rights reserved. "
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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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    • "© Permanyer Publications 2011 Table 1. Humanized mouse models and topical listing of HIV-related references CD34 + transplanted humanized mice Mouse strain/ humanized mouse DKO* NOG* NSG* BLT † In vivo HIV replication and pathogenesis Baenziger, 2006 Berges, 2006 An, 2007 Gorantla, 2007 Zhang, 2007 Berges, 2008 Hofer, 2008 Jiang, 2008 Van Duyne, 2008 Berges, 2009 Choudhory, 2009 Ince, 2009 Hofer, 2010 Sango, 2010 Neff, 2010 Luo, 2010 Neff, 2011 Watanabe, 2007^ Watanabe, 2007^ Nie, 2009 Sato, 2010 Sato, 2010 Van Duyne, 2008 Kumar, 2008 Gorantla, 2010 Gorantla, 2010 Holt, 2010 Joseph, 2010^ Dash, 2011 Sun, 2007 Denton, 2008 Brainard, 2009 Denton, 2010 Kim, 2010 Garg, 2011 "
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