TY - JOUR
T1 - Development of a novel transgenic mouse/SCID-hu mouse system to characterize the in vivo behavior of reservoirs of human immunodeficiency virus type 1-infected cells
AU - Wang, Emilie Jeanne
AU - Pettoello-Mantovani, Massimo
AU - Anderson, Christina M.
AU - Osiecki, Kristin
AU - Moskowitz, Devorah
AU - Goldstein, Harris
N1 - Funding Information:
Financial support: National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH; NS-39201); National Institute of Allergy and Infectious Diseases, NIH (AI-48466).
PY - 2002/11/15
Y1 - 2002/11/15
N2 - To develop a system in which transgenic and knockout technologies are used to study the in vivo behavior of human immunodeficiency virus type 1 (HIV-1) reservoirs, 2 different mouse models were combined: transgenic mice carrying full-length provirus encoding the monocytetropic HIV-1JR-CSF isolate (JR-CSF mice) and severe combined immunodeficient mice implanted with human fetal thymus and liver tissues (thy/liv-SCID-hu mice). Extensive HIV-1 infection of human thymic implants occurred after injection of JR-CSF mouse leukocytes into thy/liv-SCID-hu mice, indicating that these cells provide an in vivo source of replicationcompetent HIV-1. In vivo persistence of transferred JR-CSF mouse leukocytes carrying replication-competent HIV-1 in thy/liv-SCID-hu mice was indicated by the emergence of HIV-1 infection in mice that had no detectable HIV-1 infection until after highly active antiretroviral therapy. Thus, thy/liv-SCID-hu mice populated with JR-CSF mouse leukocytes, a persistent cellular reservoir harboring replication-competent HIV-1, present a new in vivo system for characterizing reservoirs of HIV-1 and evaluating therapeutic strategies designed to eliminate them.
AB - To develop a system in which transgenic and knockout technologies are used to study the in vivo behavior of human immunodeficiency virus type 1 (HIV-1) reservoirs, 2 different mouse models were combined: transgenic mice carrying full-length provirus encoding the monocytetropic HIV-1JR-CSF isolate (JR-CSF mice) and severe combined immunodeficient mice implanted with human fetal thymus and liver tissues (thy/liv-SCID-hu mice). Extensive HIV-1 infection of human thymic implants occurred after injection of JR-CSF mouse leukocytes into thy/liv-SCID-hu mice, indicating that these cells provide an in vivo source of replicationcompetent HIV-1. In vivo persistence of transferred JR-CSF mouse leukocytes carrying replication-competent HIV-1 in thy/liv-SCID-hu mice was indicated by the emergence of HIV-1 infection in mice that had no detectable HIV-1 infection until after highly active antiretroviral therapy. Thus, thy/liv-SCID-hu mice populated with JR-CSF mouse leukocytes, a persistent cellular reservoir harboring replication-competent HIV-1, present a new in vivo system for characterizing reservoirs of HIV-1 and evaluating therapeutic strategies designed to eliminate them.
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U2 - 10.1086/344737
DO - 10.1086/344737
M3 - Article
C2 - 12404156
AN - SCOPUS:0037111087
SN - 0022-1899
VL - 186
SP - 1412
EP - 1421
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -