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Simian immunodeficiency virus resistance of macaques infused with interferon -engineered lymphocytes

CEA, Service de Neurovirologie (DSV/DRM), CRSSA, Institut Paris-Sud sur les Cytokines, BP 6, 92265 Fontenay aux Roses, Cedex, France¹
Equipe de l’Interféron et des Cytokines, UMR 146 CNRS, Institut Curie, Bâtiment 110, Centre Universitaire, 91405 Orsay, France²

Author for correspondence: Evelyne Lauret. Present address: U362 INSERM, Institut Gustave Roussy, PR1, 39 rue Camille Desmoulins, 94800 Villejuif, France. Fax +33 1 42 11 52 40. e-mail elauret{at}igr.fr

To test the in vivo anti-simian immunodeficiency virus (SIV) efficacy of interferon (IFN)--engineered lymphocytes, peripheral blood lymphocytes harvested from two uninfected macaques were transduced with a retroviral vector carrying a constitutively expressed IFN- gene and reinfused, resulting in approximately 1 IFN--transduced cell out of 1000 circulating cells. The gene-modified cells were well tolerated and could be detected for at least 74 days without causing any apparent side effects. These two animals together with three untreated control macaques were then infected with SIVmac251. The two IFN--infused macaques are in good health, 478 days after infection, with a reduced plasma virus load and sustained numbers of CD4⁺ and CD8⁺ cells. Throughout the study, the proportion of IFN--transduced cells has been maintained. Of the three control macaques, two were characterized by a high plasma virus load and a decrease in CD4⁺ cells. One was moribund and was sacrificed 350 days after infection and the other now has fewer than 100 circulating CD4⁺ cells/ml. Unexpectedly, the third control macaque, which, like the two IFN--infused animals, had a low plasma virus load and a maintenance of CD4⁺ and CD8⁺ cell number, was characterized by a permanent level of serum IFN-, of unknown origin, already present before SIV infection. Although no definite conclusion can be made in view of the limited number of animals, these data indicate that further exploration is warranted of an IFN--based anti-human immunodeficiency virus gene therapy.

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