HIV-1 INFECTION KINETICS IN TISSUE-CULTURES

Despite intensive experimental work on HIV-1, very little theoretical work has focused on HIV-1 spread in tissue culture. This article uses two systems of ordinary differential equations to model two modes of v iral spread, cell-free virus and cell-to-cell contact. The two models produce remarkably similar qualitative results. Simulations using real istic parameter regimes showed that starting with a small fraction of cells infected, both cell-free viral spread and direct cell-to-cell tr ansmission give an initial exponential phase of viral growth, followed by either a crash or a gradual decline, extinguishing the culture. Un der some conditions, an oscillatory phase may precede the extinction. Some previous models of in vivo HIV-1 infection oscillate, but only in unrealistic parameter regimes. Experimental tissue infections sometim es display several sequential cycles of oscillation, however, so our m odels can at least mimic them qualitatively. Significantly, the models show that infective oscillations can be explained by infection dynami cs; biological heterogeneity is not required. The models also display proportionality between infected cells and cell-free virus, which is r eassuringly consistent with assumptions about the equivalence of sever al measures of viral load, except that the proportionality requires a relatively constant total cell concentration. Tissue culture parameter values can be determined from accurate, controlled experiments. There fore, if verified, our models should make interpreting experimental da ta and extrapolating it to in vivo conditions sharper and more reliabl e. (C) Elsevier Science Inc., 1996