Lapenta Caterina, Spada Massimo, Santini Stefano M, Racca Sara, Dorigatti Fernanda, Poli Guido, Belardelli Filippo, Alfano Massimo
Department of Cellular Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy.
Int Immunol. 2005 Apr;17(4):469-75. doi: 10.1093/intimm/dxh226. Epub 2005 Mar 3.
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.
百日咳博德特氏菌毒素B寡聚体（PTX - B）已被证明在体外可抑制HIV感染和复制。本文在HIV感染的体内替代模型中测试了PTX - B的潜在抗病毒作用，即用人外周血白细胞（PBL）重建的SCID小鼠（hu - PBL - SCID），并感染CCR5依赖型（R5）HIV - 1毒株。腹腔内（i.p.）接种PTX - B然后感染R5毒株SF - 162的SCID小鼠在7天后处死，并分析人PBL（hu - PBL）淋巴组织重建、hu - PBL感染、血浆病毒血症以及从体外培养的腹腔内hu - PBL中拯救病毒的情况。与每只动物给予500 ng PTX - B处理的小鼠未显示病毒抑制迹象不同，每日给予PTX - B（每只小鼠50 ng）强烈抑制病毒感染和复制，这通过大多数动物中检测不到病毒血症、不存在感染的hu - PBL以及无法拯救出感染性HIV来确定。此外，在感染前2小时和感染后两次注射PTX - B可防止所有（10/10）受试动物感染HIV - 1并抑制其复制。因此，PTX - B在hu - PBL - SCID小鼠中有效抑制病毒感染和复制，支持了它可能代表一种抗HIV - 1感染新药的假说。
