The binding subunit of pertussis toxin inhibits HIV replication in human macrophages and virus expression in chronically infected promonocytic U1 cells

We have recently shown that the binding subunit of pertussis toxin (PTX-B) inhibits the entry and replication of macrophage-tropic (R5) HIV-1 strains in activated primary T lymphocytes. Furthermore, PTX-B suppressed the repli cation of T cell-tropic (X4) viruses at a postentry level in the same cells , In this study we demonstrate that PTX-B profoundly impairs entry and repl ication of the HIV-1(ADA) (R5), as well as of HIV pseudotyped with either m urine leukemia virus or vesicular stomatitis virus envelopes, in primary mo nocyte-derived macrophages. In addition, PTX-B strongly inhibited X4 HIV-1 replication in U937 promonocytic cells and virus expression in the U937-der ived chronically infected U1 cell line stimulated with cytokines such as TN F-alpha and IL-6. Of interest, TNF-alpha -mediated activation of the cellul ar transcription factor NF-kappaB was unaffected by PTX-B. Therefore, PTX-B may represent a novel and potent inhibitor of HIV-1 replication to be test ed for efficacy in infected individuals. In support of this proposition, a genetically modified mutant of PTX (PT-9K/129G), which is safely administer ed for prevention of Bordetella pertussis infection, showed an in vitro ant i-HIV profile superimposable to that of PTX-B.