Pertussis toxin and its binding unit inhibit HIV-1 infection of human cervical tissue and macrophages involving a CD14 pathway |
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Authors: | Hu Qinxue Younson Justine Griffin George E Kelly Charles Shattock Robin J |
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Institution: | Center for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London SW17 0RE, UK. |
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Abstract: | Pertussis toxin (PTX) and its binding unit (PTX-B) have been shown to inhibit human immunodeficiency virus (HIV)-1 infection of primary cells. However, the anti-HIV mechanisms have yet to be defined. We demonstrate that PTX inhibits HIV-1 infection of human cervical tissue independently of viral tropism. PTX-B showed a similar pattern of HIV-1 inhibition. Further investigation in macrophages demonstrated that PTX/PTX-B inhibited HIV-1 expression but that other G protein inhibitors and activators had no effect on HIV-1 replication. Unlike the anti-HIV bacterial lipopolysaccharide, the anti-HIV effects of PTX/PTX-B were not due to beta -chemokine production or coreceptor down-modulation, but they were dependent on interaction with cell-surface receptors. Antibody blocking studies suggested that cell-surface CD14 is very likely to be the principal receptor involved in the anti-HIV effects of PTX/PTX-B. This was further strengthened by the results of surface plasmon resonance analyses. Further definition of the mechanisms of such inhibition may lead to the development of novel HIV-1 prevention strategies. |
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