AEGiS-12IAC: Transmission of immature HIV-1 during protease inhibitor treatment or by mutants in the viral protease.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Transmission of immature HIV-1 during protease inhibitor treatment or by mutants in the viral protease.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:8-9 (abstract no. 11132)

Potash MJ, Krachmarov C, Bentsman G, Volsky DJ
St Lukes-Roosevelt/Columbia University, New York, USA.

OBJECTIVE: To evaluate the requirement for mature HIV-1 for cell-cell virus transmission.

METHODS: HIV-1 chronically infected cells were cultured in the presence or absence of the viral protease (PR) inhibitor, Ro 31-8959 (saquinavir), and transmission of HIV-1 by cell-free virus and by co-cultivation with uninfected cells were evaluated by the MAGI assay for Tat-mediated expression of beta-galactosidase, by detection of HIV-1 antigens by immunofluorescence staining or by Elisa for p24, and by analysis of viral protein structure by electrophoresis and Western blotting. Alternatively, cell-free and cell-cell transmission of an HIV-1 mutant in the viral PR (SVC-P2) were similarly evaluated.

RESULTS: When viral PR was inhibited by Ro 31-8959 or was inactivated by mutation, HIV-1 transmission by cell-free virus was reduced 100-350 fold. However transmission of HIV-1 by cocultivation in the absence of PR activity was reduced only 2-20 fold. Western blot analysis of preintegration complexes in cell nuclei confirmed the absence of mature viral matrix protein during transmission by cocultivation in the presence of Ro 31-8959.

CONCLUSION: HIV-1 synthesized during PR inhibition or inactivation retains infectivity and can be transmitted by cell-cell contact.

Keywords: AEGIS, HIV-1, Protease Inhibitors, Endopeptidases, Saquinavir, HIV Protease, HIV-1 Reverse Transcriptase, Blotting, Western, Greece, transmission, therapy, virology, ICA12
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