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-S...

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Bibliographic Details
Published in:International immunology 2005-04, Vol.17 (4), p.469-475
Main Authors: Lapenta, Caterina, Spada, Massimo, Santini, Stefano M., Racca, Sara, Dorigatti, Fernanda, Poli, Guido, Belardelli, Filippo, Alfano, Massimo
Format: Article
Language:English
Subjects:
Animals
Anti-HIV Agents - pharmacology
anti-viral
Bordetella pertussis
Dose-Response Relationship, Drug
Female
HIV Infections - drug therapy
HIV-1 - drug effects
hu-PBL    human peripheral blood leukocytes
Human immunodeficiency virus 1
Humans
i.p.    intra-peritoneal
Leukocytes - virology
LN    lymph nodes
MDM    monocyte-derived macrophages
Mice
Mice, SCID
MW    molecular weight
P1    protocol P1
P2    protocol P2
PBL    peripheral blood leukocytes
Pertussis Toxin - pharmacology
PTX-B    pertussis toxin B-oligomer
PTX    pertussis toxin
R5 HIV-1
SIV    simian immunodeficiency virus
Virus Replication - drug effects
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Summary: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.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxh226