The C-terminal 26-residue peptide of serpin A1 is an inhibitor of HIV-1.
Serpin A1 (alpha1-proteinase inhibitor) inhibits human immunodeficiency virus 1 (HIV-1) production by mechanisms which remain to be elucidated. The complex formation of serpin A1 with proteinases eliminates the proteolytic activity and generates a fragment corresponding to the serpin C-terminal 36-residue peptide. Here, we show that the C-terminal 26-residue peptide of serpin A1 (A1-C26) inhibits HIV-long terminal repeat (LTR)-driven transcription in epithelial cells transfected with HIV-1 LTR promoter-driven genes. A1-C26 increased STAT1 phosphorylation and strongly reduced viral expression in a monocytic cell line infected with HIV-1 NL4-3. This reduction of expression was also observed in HIV-1 infected, PHA-activated peripheral blood mononuclear cells. In HIV-1 infected cells, the inhibitory activity of HIV-1 caused by B9-C23 and C1-C26, the A1-C26 homologues corresponding to the C-terminal sections of serpin B9 and serpin C1, was much lower than that obtained with A1-C26. These serpin peptides represent a novel class of antiviral agents.
Congote
Luis Fernando
LF
Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, ouest, Montreal, Canada H3A 1A1. luis.f.congote@muhc.mcgill.ca
D000998:Antiviral Agents / Q000008:administration & dosage*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage*; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects*; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage*
D000998:Antiviral Agents; D010446:Peptide Fragments; D010455:Peptides; D000515:alpha 1-Antitrypsin; C510194:serpin A1 (A1-C26), human