HIV p17 enhances lymphocyte proliferation and HIV-1 replication after binding to a human serum factor

Objective: To analyse the role of recombinant HIV-1 protein p17 in the modulation of cell activity. Methods: Peripheral blood mononuclear cells (PBMC) obtained from healthy donors were cultured in the presence or absence of p17 with mitogens such as phytohaemagglutinin or interleukin-2 and their response assayed by cell proliferation. Cross-linking experiments were employed to investigate the presence of a binding between p17 and factor(s) present in human serum. An immunoenzymatic assay for p24 antigen detection was used to analyse the effect of the addition of exogenous p17 to cultures of PBMC infected with HIV-1 in vitro. Results: Purified recombinant p17 protein at a concentration of 0.25 mu g/ml significantly increased the proliferation of preactivated PBMC obtained from healthy donors. This effect was obtained by binding p17 to factor( s) present in human serum and observed on both CD4+ and CD8+ T cells. Recombinant p17 also induced an increased rate of HIV-1 replication, probably due to enhanced T-cell proliferation. The activity of p17 protein was inhibited by anti-p17 antibodies generated by injecting recombinant p17 in rabbits, but not by human antibodies generated during the natural course of HIV infection. Conclusion: Characterization of the human factor( s) and identification of the interacting p17 epitope( s) will improve our understanding of the mechanisms used by HIV to efficiently replicate in our organisms.