Pertussis toxin B-oligomer inhibits HIV infection and replication in hu-PBL-SCID mice.
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.
Lapenta
Caterina
C
Department of Cellular Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy.
Spada
Massimo
M
Santini
Stefano M
SM
Racca
Sara
S
Dorigatti
Fernanda
F
Poli
Guido
G
Belardelli
Filippo
F
Alfano
Massimo
M
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D037342:Pertussis Toxin / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D037342:Pertussis Toxin