Alpha-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 alpha-melanocyte-stimulating hormone (alpha-MSH) and its C-terminal tripeptide [alpha-MSH (11-13), KPV] alter HIV expression in infected cells. The results indicate that chronically HIV-1-infected promonocytic U1 cells produce alpha-MSH and that immunoneutralization of the endogenous peptide enhances HIV expression. Because U1 cells express the alpha-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 alpha-MSH peptides on HIV expression, we measured p24 antigen release by TNF-alpha-stimulated U1 cells exposed to a wide range of concentrations of synthetic alpha-MSH and KPV. Viral expression was reduced by both peptides. KPV also effectively reduced HIV replication in acutely infected monocyte-derived macrophages (MDM). The basis of the peptide influence on viral replication is at the transcriptional level; KPV inhibited activation of NF-kappaB that is known to enhance viral expression. Endogenous alpha-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.
Barcellini
W
W
Division of Hematology, Ospedale Maggiore di Milano IRCCS, Italy.
Colombo
G
G
La Maestra
L
L
Clerici
G
G
Garofalo
L
L
Brini
A T
AT
Lipton
J M
JM
Catania
A
A
D004279:DNA, Viral / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology
D004279:DNA, Viral; D016655:HIV Core Protein p24; D016328:NF-kappa B; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C083236:alpha-MSH (1-13), Val(13)-; D000521:alpha-MSH; C043156:MSH (11-13); D009074:Melanocyte-Stimulating Hormones