6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in cultures and role of possible cofactors.

Int Conf AIDS 1990 Jun 20-23; 6:332 (abstract no. 1072)
Lemaitre M, Guetard D, Blanchard A, Henin Y, Montagnier L, Zerial A; Rhone-Poulenc SANTE, CRVA, Vitry/Seine, France

OBJECTIVE: We have analysed the activity of several tetracycline analogues on HIV-infected cells.

METHODS: We have tested these compounds as HIV replication inhibitors in CEM clone 13 cells and in human peripheral blood lymphocytes (PBL). We have measured the reduction of cytopathic effect (CPE) induced by HIV-1 (LAV-bru strain) - MTT assay - and reduction of reverse transcriptase (RT) activity in supernatants. We have also tested the TCID50 and cytopathogenicity of HIV stocks produced in the presence of the compounds.

RESULTS: Minocycline and doxycycline were the most active ones in inhibiting the virus induced CPE between 7 and 14 days post infection. The active concentrations (0.3-2.5 mug/ml) were devoid of toxicity in uninfected cultures. Virus production was not inhibited. Protected cells produced RT and infectious virus in their supernatant for several weeks even if the compounds were removed. In the later case, reappearance of cell lysis was not observed. Infectious HIV stocks produced in the presence of tetracycline analogs had definitely lost the capacity of inducing cell lysis.

CONCLUSIONS: Our results indicate a dissociation between protection against CPE and inhibition of replication. We suggest that the cytopathogenicity of HIV may be due, in some cases, to the presence of tetracycline-sensitive contaminants. We study the nature of this cofactor and the activity of other possible inhibitors.

Keywords: AEGIS, HIV, Tetracyclines, Tetracycline, Virus Replication, HIV-1, RNA-Directed DNA Polymerase, Reverse Transcriptase Inhibitors, Antiviral Agents, HIV Core Protein p24, HIV Infections, Doxycycline, Lymphocytes, HIV Seropositivity, Antibiotics, Human, virology, ICA6

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