TY - JOUR
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 J.
AU - West, John T.
AU - Wood, Charles
AU - Dewhurst, Stephen
AU - Gendelman, Howard E.
AU - Poluektova, Larisa
PY - 2007/3
Y1 - 2007/3
N2 - 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.
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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U2 - 10.1128/JVI.02010-06
DO - 10.1128/JVI.02010-06
M3 - Article
C2 - 17182671
AN - SCOPUS:33947356676
SN - 0022-538X
VL - 81
SP - 2700
EP - 2712
JO - Journal of virology
JF - Journal of virology
IS - 6
ER -