It's one thing to administer recombinant interferon as antiviraltherapy. Educating cells to make their own do-it-yourself interferon issomething else.A team of French scientists reports doing just that to hamstring theAIDS virus. Their paper in the current Proceedings of the NationalAcademy of Sciences (PNAS) describes: "Blocking of retroviralinfection at a step prior to reverse transcription in cells transformed toconstitutively express interferon b."The group's leader, Edward DeMaeyer of France's National ScientificResearch Institute (INRA) stated, "We are developing methods forsomatic-cell gene therapy directed against infection with humanimmunodeficiency virus ...through the constitutive production ofautocrine interferon (IFN)."His strategy aims to block HIV at its earliest stages of cell entry andreplication, rather than the later stages at which interferon iscommonly thought to act.For starters, the team transfected various mouse and human cell lineswith IFN genes. These transformed cells synthesized interferon at aconstant low rate; their replication and survival were the same as incontrol cells. When challenged with various retroviruses, theymarkedly reduced the number of virally infected cells.Then the team assailed CEM cells with HIV viral particles. (CEM is amodel human T-cell line derived from patients with leukemia.) "Twodays later," as DeMaeyer reported, "the presence of HIV-1 proviralDNA was significantly lower in the human IFN-b transformed cellsthan in the control cells, indicating an early block of the infectiouscycle."Six hours after the onset of infection, 40 to 80 percent of the viralparticles could still be found in the transformed cells' culture medium,whereas 90 percent of the control cells' virions had moved on to infectother cells. But the transformed CEM cells died within a week or so."These findings," DeMaeyer concluded, are encouraging for the use ofthe ...IFN-b vector to explore the possibility of developing an anti-HIV-b-directed somatic cell gene therapy." Richard Mulligan at MIT'sWhitehead Institute of Biomedical Research supplied the vectorplasmids to the French investigators.SInce submitting his findings to PNAS last September, DeMaeyer hasdetermined that virus-resistant, inferferon-synthesizing CEM cells"survive for as long as 80 days. Maybe they lived even longer," he toldBioWorld in a telephone interview, "but that's when we stopped theexperiment."Moreover, moving from off-the-shelf CEM cell lines, he and his grouphave shown "that the same effect is obtained in fresh peripheral bloodlymphocytes taken from people. Of course," he added, "this is moresignificant in terms of somatic gene therapy. That's the cell that onewants eventually to protect in the body."The next step, he said, is to proceed from in vitro to in vivo testing."We want to collaborate with a group that has the rhesus monkeymodel going, infectable with the simian immune deficiency virus,SIV." He is already in discussion with one such research center, but isstill open to other offers.DeMaeyer cited three goals of such testing: First, to show that it worksin vivo; second, to determine that the transformed cell'simmunological function is not impaired; third, to solve the problem of"getting enough of those interferon-transformed, virus-resistant cellsinto the body of a seropositive person infected with AIDS."

-- David N. Leff Science Editor

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