A model of enhancement and inhibition of HIV infection of monocytes by antibodies against HIV

Antibodies (Ab) specific for epitopes on HIV glycoprotein gp120 or gp41 can inhibit or enhance HIV infection of human cellsin vitro. These effects may have significant implications both for the pathogenesis of chronic HIV infection and for vaccine development. A particularly puzzling findingin vitro is antibody dependent enhancement (ADE) at low concentrations of Ab while high concentrations of the same antibody inhibit infection. Similar phenomena have been observed for other enveloped viruses. Antibodies can inhibit infection by several mechanisms. However, by binding to receptors on target cells, virus bound antibodies can also enhance adhesion to these cells and thereby facilitate infection. We propose a mathematical model that describes how these two processes interact and hereby provide an explanation for the observed enhancement/neutralization phenomena. Simulation results were validated with good agreement against empirical data from antibody dependent enhancement of HIV infection of monocytoid (U937) cellsin vitro, and the model should be applicable to otherin vitro systems involving different cells and viruses.