AEGiS-07IAC: Decreased HIV-1 infectivity after in vitro down-regulation of CD4 with phorbol 12-myristate 13-acetate (PMA).

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

Decreased HIV-1 infectivity after in vitro down-regulation of CD4 with phorbol 12-myristate 13-acetate (PMA).

Int Conf AIDS 1991 Jun 16-21; 7:95 (abstract no. M.A.1013)
Sanhadji K, Benard I, Touraine JL; Faculte de Medecine A. Carrel, INSERM U.80-CNRS URA 1177, Rue Guillaume Paradin, 69008 Lyon, France

OBJECTIVE: To analyze the variation of HIV infectivity of lymphocytes when CD4 expression is modulated by in vitro pre-treatment with PMA.

METHODS: The MT4 cell line (3x10(5) cells/ml) was pre-treated with 1.6x10(-8) M of PMA (or with control solution) for 0.5, 1, 5 or 20 hrs, then washed and assayed for CD4 expression by cytofluorometry. The cells were then incubated with HIV-1 for 1 hr and immediately cultured. Infection was determined by cytopathogenic effect (CPE), reverse transcriptase (RT) activity and P24 antigen release in supernatant.

RESULTS: Over 80% of cells initially expressed the OKT 4A epitope. This expression decreased following PMA treatment and the lowest value was observed at 1hr (6%). A partial re-expression was however observed when the incubation period was extended to 20 hrs. The RT activity was decreased by this pre-treatment but it was even lower after 5-20 hrs of incubation than after 1 hr. This observation was confirmed by the CPE appearance and the P24 antigen release in culture supernatant. HIV-1 infectivity therefore decreased with the reduced OKT 4A expression resulting from PMA treatment but it continued to decrease when OKT 4A was re-expressed.

CONCLUSION: Although PMA increases production of several cytokines and augments HIV replication in already infected cells, this agent reduces the infectivity of cells when it is introduced in the culture before HIV. This effect is very likely to result from down-regulation of CD4 expression and it lasts even longer than the inhibition of expression of this virus receptor.

Keywords: AEGIS, Antigens, CD4, HIV-1, Down-Regulation, Tetradecanoylphorbol Acetate, HIV Core Protein p24, RNA-Directed DNA Polymerase, Virus Replication, Amphetamines, Antigens, CD, HIV, HIV Envelope Protein gp41, Receptors, HIV, HIV Infections, HIV Antibodies, Cell Line, 4-methoxyamphetamine, CD9 antigen, In Vitro, genetics, virology, ICA7
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