AEGiS-06IAC: HIV-I-induced expression of P-glycoprotein.

6th International AIDS Conference

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

HIV-I-induced expression of P-glycoprotein.

Int Conf AIDS 1990 Jun 20-23; 6:330 (abstract no. 1067)
Gupta S, Tsuruo T, Gollapudi S; University of California, Irvine, California, USA

OBJECTIVE: The expression of a 170 kD molecule, the P-glycoprotein (P-gp), is associated with decreased plasma membrane potentials and rapid drug efflux resulting in acquired multidrug resistance in cancer cells. Therefore, in this investigation, we examined whether HIV induces an over expression of P-gp that would be associated with decreased intracellular accumulation of AZT resulting in resistance to AZT.

METHODS: A T cell line (H9) and a monocyte cell line (U 937) were infected in vitro with HIV isolate. The infection was confirmed by reverse transcriptase activity, P24 antigen, and the expression of gp-120 envelope protein at cell surface. Infected and control uninfected cells were analyzed flow cytometrically for plasma membrane potentials using DIOC5 dye, daunorubicin accumulation, and for the expression of P-gp with monoclonal antibody MRK-16. 3H AZT accumulation was measured by scintillation counter. Data of plasma membrane potentials and daunorubicin accumulation are presented as mean fluorescence channel numbers (MFC) and 3H AZT accumulation as counts per minute (cpm).

RESULTS: The plasma membrane potentials of infected cells were decreased (H9= 175, U937= 281 MFC) as compared to uninfected cells (H9= 296, U937= 505 MFC). Both H9 and U937 HIV infected cells expressed increased levels of P-gp as compared to uninfected cells. 3H AZT accumulation was lower in infected cells (H9= 416, U937= 1224 cpm) as compared to uninfected cells (H9= 148, U937= 3918 cpm). Daunorubicin accumulation was also lower in infected cells (H9=920, U937=587 MFC) as compared to uninfected cells (H9=1162, U937=971 MFC).

CONCLUSION: HIV-1 induces depolarization of plasma membrane, increased expression of P-gp, and decreased intracellular accumulation of drug. Data suggest that HIV-induced expression of p-gp may be one of the mechanisms for the development of resistance to AZT and perhaps other agents used in the treatment of HIV infection in vivo.

Keywords: AEGIS, HIV-1, Zidovudine, Phosphatidylserines, HIV Infections, Glycoproteins, RNA-Directed DNA Polymerase, HIV-1 Reverse Transcriptase, Daunorubicin, Reverse Transcriptase Inhibitors, Anti-HIV Agents, P-Glycoprotein, Cell Line, T-Lymphocytes, Drug Resistance, Multiple, Membrane Glycoproteins, Monocytes, In Vitro, ICA6

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