Macaque lymphocytes transduced by a constitutively expressed interferon beta gene display an enhanced resistance to SIVmac251 infection.

作者: Franck Matheux , Roger Le Grand , Veronique Rousseau , Edward De Maeyer , Dominique Dormont

DOI: 10.1089/10430349950018878

关键词:

摘要: We are developing a method of gene therapy HIV infection based on the low constitutive expression an interferon beta (IFN-beta) in target cells. Herein we report first step development relevant animal model, provided by macaque (Macaca fascicularis) infected with pathogenic SIVmac251 isolate. To avoid possibility vivo rejection lymphocytes expressing Hu IFN-beta, have PCR-amplified and sequenced Ma IFN-beta-coding sequence, placed it under control PstI-NruI 0.6-kb fragment murine H-2Kb promoter MFG-K(b)MaIFNbeta retroviral vector. Lymphocytic CEMX174 cells, transduced coculture packaging cells this construct, harbored mean 0.07 to 1.2 copies IFN-beta transgene per cell, were characterized IFN production ranging from 75 750 units 5 x 10(5) 3 days. The IFN-beta-transduced populations displayed enhanced resistance against Control experiments showed that could not be ascribed released during days or mere transduction Macaque vector acquired number cell 0.03 0.1. Such led release into culture medium, 10 20 This increased anti-SIV lymphocytes, as demonstrated decreased p27 antigen without affecting lymphocyte proliferation.

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