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

Harris Goldstein, Massimo Pettoello-Mantovani, Christina M. Anderson, Pierre Cordelier, Roger J. Pomerantz, David S. Strayer

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1425-1430
Number of pages6
JournalJournal of Infectious Diseases
Volume185
Issue number10
DOIs
StatePublished - May 15 2002

Fingerprint

Severe Combined Immunodeficiency
Simian virus 40
Virus Diseases
Genetic Therapy
HIV-1
Liver
SCID Mice
Thymocytes
Transplants
Viruses
Integrases
Gene Transfer Techniques
Immunoglobulin Fragments
Leukocytes
Genes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

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. / Goldstein, Harris; Pettoello-Mantovani, Massimo; Anderson, Christina M.; Cordelier, Pierre; Pomerantz, Roger J.; Strayer, David S.

In: Journal of Infectious Diseases, Vol. 185, No. 10, 15.05.2002, p. 1425-1430.

Research output: Contribution to journalArticle

@article{630427666bc34780b3b6b68a90a954ab,
title = "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",
abstract = "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.",
author = "Harris Goldstein and Massimo Pettoello-Mantovani and Anderson, {Christina M.} and Pierre Cordelier and Pomerantz, {Roger J.} and Strayer, {David S.}",
year = "2002",
month = "5",
day = "15",
doi = "10.1086/340210",
language = "English (US)",
volume = "185",
pages = "1425--1430",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - 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

AU - Goldstein, Harris

AU - Pettoello-Mantovani, Massimo

AU - Anderson, Christina M.

AU - Cordelier, Pierre

AU - Pomerantz, Roger J.

AU - Strayer, David S.

PY - 2002/5/15

Y1 - 2002/5/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037093953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037093953&partnerID=8YFLogxK

U2 - 10.1086/340210

DO - 10.1086/340210

M3 - Article

VL - 185

SP - 1425

EP - 1430

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 10

ER -