Pertussis toxin B-oligomer inhibits HIV infection and replication in hu-PBL-SCID mice

Abstract

Bordetella pertussis toxin B-oligomer (PTX-B) has been shown to inhibit HIV infection and replication in vitro. The potential anti-viral effect of PTX-B was tested here in an in vivo surrogate model of HIV infection, i.e. SCID mice reconstituted with human peripheral blood leukocytes (PBL) (hu-PBL-SCID) and infected with a CCR5-dependent (R5) HIV-1 strain. SCID mice inoculated intra-peritoneal (i.p.) with PTX-B and then infected with the R5 strain SF-162 were sacrificed 7 days later and analyzed for human PBL (hu-PBL) lymphoid tissue reconstitution, infection of hu-PBL, plasma viremia and viral rescue from ex vivo-cultivated i.p. hu-PBL. Unlike mice treated with 500 ng per animal of PTX-B showing no evidence of viral inhibition, daily administration of PTX-B (50 ng per mouse) strongly inhibited virus infection and replication, as determined by undetectable viremia, absence of infected hu-PBL and lack of rescue of infectious HIV in most animals. Furthermore, PTX-B injection 2 h before and twice after infection prevented HIV-1 infection and replication in all (10/10) tested animals. Thus, PTX-B potently inhibited virus infection and replication in hu-PBL-SCID mice, supporting the hypothesis that it may represent a new pharmacological agent against HIV-1 infection.

Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

“…These results support the hypothesis that PTX-B or related molecules, such as the genetically modified PT-9K/129G (83), which retains all the HIV inhibitory features of PTX-B (9,26,84), could represent potent new pharmacological agents against HIV infection, as we have also recently demonstrated in infected lymphoid histocultures (85) and hu-PBL SCID mice infected with HIV (86).…”

Pertussis toxin B-oligomer dissociates T cell activation and HIV replication in CD4 T cells released from infected lymphoid tissue

“…In support of this interpretation, as we observed in a parallel study, PTX-B inoculation of SCIDhu PBL mice either prevented or curtailed HIV infection and/or virus replication as a function of the schedule of administration and of the dose of PTX-B [27].…”

Pertussis Toxin and Adenylate Cyclase Toxin: Key Virulence Factors of Bordetella Pertussis and Cell Biology Tools

“…In another study, PTB inhibited HIV infection of human cervical tissue, and the surface molecule CD14 was found to be the principal receptor for PTB in these effects [58]. Furthermore, in a surrogate animal model of HIV infection (severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes), injection of PTB strongly inhibited HIV infection and replication [59], and PTB promoted the proliferation of HIV-infected T lymphocytes from human tonsillar tissue without triggering virus replication [60]. However, whether PTB can be advanced as a potential therapeutic agent in human HIV disease remains to be determined.…”