title: The binding subunit of pertussis toxin inhibits HIV replication in human macrophages and virus expression in chronically infected promonocytic U1 cells.
abstract: 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 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-1(ADA) (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-alpha and IL-6. Of interest, TNF-alpha-mediated activation of the cellular 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 tested for efficacy in infected individuals. In support of this proposition, a genetically modified mutant of PTX (PT-9K/129G), which is safely administered for prevention of Bordetella pertussis infection, showed an in vitro anti-HIV profile superimposable to that of PTX-B.
authors.affiliation: AIDS Immunopathogenesis Unit, Department of Biology and Technology, and Laboratory of Clinical Immunology, Division of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy. massimo.alfano@hsr.it
authors.forename: M
authors.initials: M
authors.lastname: Alfano
authors.forename: G
authors.initials: G
authors.lastname: Vallanti
authors.forename: P
authors.initials: P
authors.lastname: Biswas
authors.forename: C
authors.initials: C
authors.lastname: Bovolenta
authors.forename: E
authors.initials: E
authors.lastname: Vicenzi
authors.forename: B
authors.initials: B
authors.lastname: Mantelli
authors.forename: T
authors.initials: T
authors.lastname: Pushkarsky
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.forename: M
authors.initials: M
authors.lastname: Bukrinsky
authors.forename: G
authors.initials: G
authors.lastname: Poli
mesh_terms: D000998:Antiviral Agents / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D017930:Genes, Reporter / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D037342:Pertussis Toxin; D011485:Protein Binding / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D020298:U937 Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; C028391:G protein, vesicular stomatitis virus; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; D010566:Virulence Factors, Bordetella; D008156:Luciferases; D037342:Pertussis Toxin