Effect of alpha-1 antitrypsin Portland variant (alpha 1-PDX) on HIV-1 replication.

The present work investigated the potential role of alpha-1 antitrypsin Portland variant (alpha 1-PDX), a bioengineered serine proteinase inhibitor (serpin), in the interference with the viral replication of HIV-1, induction of syncytia and maturation of envelope glycoprotein gp160 to gp120 and gp41. A Jurkat lymphoid cell line transfected with a plasmid containing the alpha 1-PDX cDNA (J-PDX) and expressing the protein in a stable manner was infected with HIV-1(Lai). Controls were Jurkat cells transfected with the same vector pcDNA3 without the cDNA insert (J-pcDNA3). The results showed that viral replication of HIV-1 was significantly inhibited with a delay in replication kinetics in J-PDX cells as compared with J-pcDNA3 cells. In addition, a comparison of the infectious capacity of viruses produced in the presence and absence of alpha 1-PDX revealed that this capacity differed. It was found that alpha 1-PDX exerts its effect by interfering with the formation of syncytia between J-PDX cells infected with gp160 recombinant vaccinia virus, or after infection by HIV-1 and co-culture with uninfected Molt-4 cells. In contrast, when the same experiments were performed with J-pcDNA3 cells, a large number of syncytia was obtained. Analysis of viral proteins by Western blotting and densitometry showed that the inhibition of the cytopathic effect of HIV-1 and viral replication was correlated with the capacity of alpha 1-PDX to interfere with the maturation of gp160 to gp120 and gp41.