The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1 replication at multiple stages

We have recently demonstrated that the binding subunit (B-oligomer) of pert ussis toxin (PTX-B) deactivates CCR5 and inhibits entry of R5 human immunod eficiency virus type 1 (HIV-1) strains in activated primary T lymphocytes ( M. Alfano et al., J. Exp. Med. 190:597-605, 1999). We now present evidence that PTX-B also affects a postentry step of HIV-1 replication. While PTX-B inhibited fusion induced by R5 but not that induced by X4 envelopes, it blo cked infection of T cells with recombinant HIV-1 particles pseudotyped with R5, X4, and even murine leukemia virus or vesicular stomatitis virus envel opes. It also suppressed HIV-1 RNA synthesis in cultures of infected periph eral blood mononuclear cells when new infections had been inhibited by zido udine, and it reduced Tat-dependent expression of the luciferase reporter g ene controlled by the HIV-1 long terminal repeat (LTR). Surprisingly, PTX-B did not affect expression from the cytomegalovirus promoter, nor did it re duce the basal (Tat-independent) expression from the LTR promoter. These re sults indicate that PTX-B inhibits HIV-1 infection at both the entry and th e postentry stages of viral replication, with the postentry activity specif ically affecting transcription or stability of Tat-stimulated HIV-1 mRNAs.