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Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells
Institution:1. Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, WRN 401, 02114, Boston, MA, USA;2. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;3. Liver Tumor Translational Research Program, Harold C. Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA;4. Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France
Abstract:Tetracycline analogs were evaluated for anti-HIV activity in CEM cells; minocycline and doxycycline were the most active of these in inhibiting the virus-induced cytopathic effect between 7 and 14 days post-infection. The active concentrations (0.3–1.5 μg/ml) were devoid of toxicity in uninfected cultures. Virus production, however, was not inhibited, indicating a dissociation between protection against cell death and suppression of virus growth. These protected cells could be maintained in culture for 6–7 weeks, even in the absence of the compounds. After that period, virus production ceased and cells could then be cultivated for several months without loss of viability or reappearance of virus production. As HIV stocks produced in the presence of tetracycline analogs were unable to induce cell death, we suggest that the cytopathogenicity of HIV may be due in some cases to the presence of tetracycline-sensitive contaminating microorganisms.
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