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International Immunology Advance Access originally published online on March 3, 2005
International Immunology 2005 17(4):469-475; doi:10.1093/intimm/dxh226
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

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

Caterina Lapenta1, Massimo Spada1, Stefano M. Santini1, Sara Racca2, Fernanda Dorigatti2, Guido Poli3,4, Filippo Belardelli1 and Massimo Alfano3,5

1 Department of Cellular Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy
2 Diagnostica e Ricerca San Raffaele s.p.a., Via Olgettina 60, 20132 Milan, Italy
3 AIDS Immunopathogenesis Unit, Department of Immunology and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy
4 Vita-Salute San Raffaele University, School of Medicine, Via Olgettina 60, 20132 Milan, Italy
5 Present address: P2-P3 Laboratories, DIBIT, Via Olgettina, 58, 20132 Milan, Italy

Correspondence to: M. Alfano; E-mail: massimo.alfano{at}hsr.it

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.

Keywords: anti-viral, R5 HIV-1

Transmitting editor: L. Moretta


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