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

M. Alfano, G. Vallanti, P. Biswas, C. Bovolenta, E. Vicenzi, B. Mantelli, T. Pushkarsky, R. Rappuoli, A. Lazzarin, M. Bukrinsky, G. Poli

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently shown that the binding subunit of pertussis toxin (PTX-B) inhibits the entry and replication of macrophagetropic (R5) HIV-1 strains in activated primary T lymphocytes. Furthermore, PTX-B suppressed the replication 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 replication of the HIV-1ADA (R5), as well as of HIV pseudotyped with either murine leukemia virus or vesicular stomatitis virus envelopes, in primary monocyte-derived macrophages. In addition, PTX-B strongly inhibited X4 HIV-1 replication in U937 promonocytic cells and virus expression in the U937-derived chronically infected U1 cell line stimulated with cytokines such as TNF-α and IL-6. Of interest, TNF-α-mediated activation of the cellular transcription factor NF-κB was unaffected by PTX-B. Therefore, PTX-B may represent a novel and potent inhibitor of HIV-1 replication to be tested for efficacy in infected individuals. In sùpport of this proposition, a genetically modified mutant of PTX (PT-gK/129G), which is safely administered for prevention of Bordetella pertussis infection, showed an in vitro anti-HIV profile superimposable to that of PTX-B.

Original languageEnglish
Pages (from-to)1863-1870
Number of pages8
JournalJournal of Immunology
Volume166
Issue number3
Publication statusPublished - Feb 1 2001

ASJC Scopus subject areas

  • Immunology

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