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-/-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.

Original languageEnglish (US)
Pages (from-to)2700-2712
Number of pages13
JournalJournal of virology
Volume81
Issue number6
DOIs
StatePublished - Mar 1 2007

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Human immunodeficiency virus 1
HIV-1
mice
Thymus Gland
busulfan
xenotransplantation
Animal Disease Models
immunoglobulin M
Active Immunotherapy
Busulfan
lymphatic diseases
umbilical cord
Heterologous Transplantation
vaccine development
Virus Diseases
cells
Humoral Immunity
virus replication
Hematopoietic Stem Cells
Fetal Blood

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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title = "Human immunodeficiency virus type 1 pathobiology studied in humanized BALB/c-Rag2-/-γc-/- mice",
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-/-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.",
author = "Santhi Gorantla and Hannah Sneller and Lisa Walters and Sharp, {John G} and Pirruccello, {Samuel Jay} and West, {John T} and Charles Wood and Stephen Dewhurst and Gendelman, {Howard Eliot} and Poluektova, {Larisa Y}",
year = "2007",
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T1 - Human immunodeficiency virus type 1 pathobiology studied in humanized BALB/c-Rag2-/-γc-/- mice

AU - Gorantla, Santhi

AU - Sneller, Hannah

AU - Walters, Lisa

AU - Sharp, John G

AU - Pirruccello, Samuel Jay

AU - West, John T

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AU - Dewhurst, Stephen

AU - Gendelman, Howard Eliot

AU - Poluektova, Larisa Y

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AB - 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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