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 Por tland variant (alpha1-PDX), a bio engineered serine proteinase inhibitor (s erpin), in the interference with the viral replication of HIV-I, induction of syncytia and maturation of envelope glycoprotein gp160 to gp120 and gp41 . A Jurkat lymphoid cell line transfected with a plasmid containing the alp ha1-PDX cDNA (J-PDX) and expressing the protein in a stable manner was infe cted with HIV-1(Lai) Controls were Jurkat cells transfected with the same v ector pcDNA3 without the cDNA insert (J-pcDNA3), The results showed that vi ral replication of HIV-I was significantly inhibited with a delay in replic ation kinetics in J-PDX cells as compared with J-pcDNA3 cells. In addition, a comparison of the infectious capacity of viruses produced in the presenc e and absence of alpha1-PDX revealed that this capacity differed. It was fo und that alpha1-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 West ern blotting and densitometry showed that the inhibition of the cytopathic effect of HIV-1 and Viral replication was correlated with the capacity of a lpha1-PDX to interfere with the maturation of gp160 to gp120 and gp41.