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Suppression of HIV-1 infection in primary CD4 T cells transduced with a self-inactivating lentiviral vector encoding a membrane expressed gp41-derived fusion inhibitor.
Perez, E E; Riley, J L; Carroll, R G; von Laer, D; June, C H.
Afiliación
  • Perez EE; Children's Hospital of Philadelphia, Division of Allergy and Immunology, Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Clin Immunol ; 115(1): 26-32, 2005 Apr.
Article en En | MEDLINE | ID: mdl-15870017
Peptidomimetics of HIV-1 gp41 sequences required for membrane fusion are potent inhibitors of HIV-1 entry. We hypothesize that expression of a membrane-bound gp41-derived fusion inhibitor will confer HIV-1 resistance to primary CD4 T cells. Efficient gene delivery and stable expression of a membrane-bound gp41-derived fusion inhibitor to primary CD4 T cells was accomplished using a self-inactivating lentiviral vector. A potent antiviral effect was observed when transduced CD4 T cells were challenged with a highly virulent CXCR4-tropic strain of HIV-1. Production of soluble p24 in the supernatant was inhibited 100-fold, and cytopathic effects were evident early in non-transduced cells and absent in transduced cells. Expression of the gp41 sequences was not detrimental to CD4 cells as transduced CD4 T cells exhibited a population doubling time that was equivalent to T cells transduced with a control vector. Results from this study support the rationale to use this lentiviral vector targeted at HIV entry as a potential gene therapy for HIV infection.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Linfocitos T CD4-Positivos / Proteína gp41 de Envoltorio del VIH / Infecciones por VIH / VIH-1 / Lentivirus Límite: Humans Idioma: En Revista: Clin Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Linfocitos T CD4-Positivos / Proteína gp41 de Envoltorio del VIH / Infecciones por VIH / VIH-1 / Lentivirus Límite: Humans Idioma: En Revista: Clin Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos