Gene therapy using a simian virus 40-derived vector inhibits the development of in vivo human immunodeficiency virus type 1 infection of severe combined immunodeficiency mice implanted with human fetal thymic and liver tissue.
To evaluate the in vivo efficacy of gene therapy for treating human immunodeficiency virus type 1 (HIV-1) infection, a novel simian virus (SV) 40-derived vector gene delivery system that efficiently transduces human leukocytes was combined with a model using severe combined immunodeficiency mice infected with HIV-1 and implanted with human fetal thymic and liver tissue (thy/liv-SCID-hu mice). The SV40-derived vector, SV(Aw), which encodes a variable fragment antibody recognizing HIV-1 integrase (IN#33),was injected into the human thymic grafts of thy/liv-SCID-hu mice and induced IN#33 expression in most of the thymocytes in the graft. After in vivo challenge with HIV-1, IN#33 expression inhibited in vivo HIV-1 infection, as evidenced by the markedly lower number of HIV-1-infected thymocytes detected in human thymic grafts injected with the SV(Aw) vector, compared with those injected with a control SV40-derived vector. Thus, these findings demonstrate the utility of this new mouse model system for assessing the in vivo efficacy of HIV-1-specific gene therapy. In addition, these data indicate that SV40-derived vectors may provide a system capable of efficient in vivo gene delivery.
Goldstein
Harris
H
Departments of Pediatrics and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. hgoldste@aecom.yu.edu
Pettoello-Mantovani
Massimo
M
Anderson
Christina M
CM
Cordelier
Pierre
P
Pomerantz
Roger J
RJ
Strayer
David S
DS
D000818:Animals; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D015483:HIV Antibodies / Q000235:genetics; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D019427:HIV Integrase / Q000276:immunology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007114:Immunization / Q000379:methods; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008099:Liver / Q000196:embryology; D016031:Liver Transplantation; D051379:Mice; D016513:Mice, SCID; D013539:Simian virus 40 / Q000235:genetics*; D013950:Thymus Gland / Q000196:embryology / Q000637:transplantation; D019076:Transgenes; D014183:Transplantation, Heterologous
D015483:HIV Antibodies; D007135:Immunoglobulin Variable Region; D019427:HIV Integrase