Pertussis Toxin and Its Binding Unit Inhibit HIV-1 Infection of Human Cervical Tissue and Macrophages Involving a CD14 Pathway

Qinxue Hu; Younson, Justine; Griffin, George E.; Kelly, Charles; Shattock, Robin J.
December 2006
Journal of Infectious Diseases;12/1/2006, Vol. 194 Issue 11, p1547
Academic Journal
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. PTXB 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 β-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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