α-Melanocyte-stimulating hormone peptides inhibit HIV-1 expression in chronically infected promonocytic U1 cells and in acutely infected monocytes

The purpose of the present research was to determine if a-melanocyte-stimulating hor- mone (a-MSH) and its C-terminal tripeptide (a-MSH (11-13), KPV) alter HIV expression in infected cells. The results indicate that chronically HIV-1-infected promonocytic U1 cells produce a-MSH and that immunoneutralization of the en- dogenous peptide enhances HIV expression. Be- cause U1 cells express the a-MSH receptor 1 (MC1R), an autocrine-inhibitory circuit based on the peptide and its receptor likely occurs in these cells. To determine effects of pharmacological concentrations of a-MSH peptides on HIV expres- sion, we measured p24 antigen release by TNF-a- stimulated U1 cells exposed to a wide range of concentrations of synthetic a-MSH and KPV. Viral expression was reduced by both peptides. KPV also effectively reduced HIV replication in acutely in- fected monocyte-derived macrophages (MDM). The basis of the peptide influence on viral replica- tion is at the transcriptional level; KPV inhibited activation of NF-kB that is known to enhance viral expression. Endogenous a-MSH likely contributes to natural defense against HIV. However, greater concentrations of synthetic peptide are much more effective in reducing HIV expression in infected cells. J. Leukoc. Biol. 68: 693-699; 2000.