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Journal of Virology, September 2000, p. 8767-8770, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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

Massimo Alfano,1,2 Tatiana Pushkarsky,1 Guido Poli,2 and Michael Bukrinsky1,*

The Picower Institute for Medical Research, Manhasset, New York 11030,1 and AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milano, Italy2

Received 28 December 1999/Accepted 8 June 2000

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.

* Corresponding author. Mailing address: The Picower Institute for Medical Research, 350 Community Dr., Manhasset, NY 11030. Phone: (516) 562-9438. Fax: (516) 365-0286. E-mail: mbukrinsky{at}picower.edu.

Journal of Virology, September 2000, p. 8767-8770, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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