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.
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 monocyte-tropic HIV-1(JR-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 replication-competent 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.
Wang
Emilie-Jeanne
EJ
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Pettoello-Mantovani
Massimo
M
Anderson
Christina M
CM
Osiecki
Kristin
K
Moskowitz
Devorah
D
Goldstein
Harris
H
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004195:Disease Models, Animal; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D019380:Anti-HIV Agents