Pertussis toxin and its binding unit inhibit HIV-1 infection of human cervical tissue and macrophages involving a CD14 pathway.
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.
Hu
Qinxue
Q
Center for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London SW17 0RE, UK.
Younson
Justine
J
Griffin
George E
GE
Kelly
Charles
C
Shattock
Robin J
RJ
D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000821:virology*; D019742:Chemokines, CC / Q000096:biosynthesis; D005260:Female; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008264:Macrophages / Q000821:virology*; D037342:Pertussis Toxin / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism / Q000494:pharmacology; D012367:RNA, Viral / Q000096:biosynthesis; D015728:Receptors, HIV / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D019742:Chemokines, CC; D016655:HIV Core Protein p24; D018950:Lipopolysaccharide Receptors; D021122:Protein Subunits; D012367:RNA, Viral; D015728:Receptors, HIV; D037342:Pertussis Toxin