The B-Oligomer of Pertussis Toxin Inhibits Human Immunodeficiency Virus Type 1 Replication at Multiple Stages

Author:

Alfano Massimo12,Pushkarsky Tatiana1,Poli Guido2,Bukrinsky Michael1

Affiliation:

1. The Picower Institute for Medical Research, Manhasset, New York 11030,1 and

2. AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milano, Italy2

Abstract

ABSTRACT We have recently demonstrated that the binding subunit (B-oligomer) of pertussis toxin (PTX-B) deactivates CCR5 and inhibits entry of R5 human immunodeficiency 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 blocked infection of T cells with recombinant HIV-1 particles pseudotyped with R5, X4, and even murine leukemia virus or vesicular stomatitis virus envelopes. It also suppressed HIV-1 RNA synthesis in cultures of infected peripheral blood mononuclear cells when new infections had been inhibited by zidovudine, and it reduced Tat-dependent expression of the luciferase reporter gene controlled by the HIV-1 long terminal repeat (LTR). Surprisingly, PTX-B did not affect expression from the cytomegalovirus promoter, nor did it reduce the basal (Tat-independent) expression from the LTR promoter. These results indicate that PTX-B inhibits HIV-1 infection at both the entry and the postentry stages of viral replication, with the postentry activity specifically affecting transcription or stability of Tat-stimulated HIV-1 mRNAs.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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