HIV-virions Appear To Be Trapped By Human Cervical Mucus

Abstract

We apply time-resolved fluorescence confocal microscopy and fluorescence correlation spectroscopy to examine the movements of fluorescently-labeled HIV-1 virions (∼120 nm) embedded in crude human cervical mucus. Particle-tracking analysis indicates that the motion of most virions is decreased 200-fold compared to that in water and is not driven by typical diffusion. Rather, the time-dependence of their ensemble-averaged mean-square displacements is proportional to τα + v2τ2, describing a combination of anomalous diffusion at short time scales (α ∼ 0.3) and flow-like behavior at longer times, τ being the lag time. We attribute the flow-like behavior to slowly-relaxing mucus matrix that follows mechanical perturbations such as stretching and twisting of the sample. Further analysis of the tracks and displacements of individual virions indicates differences in the local movements among the virions, including constrained motion and infrequent jumps, perhaps due to abrupt changes in matrix structure. We surmise that these differences are related not only to possible variations in the local microenvironments experienced by each individual virion but, perhaps, also to variations in the surface structure of the virions themselves. Possible changes in the microenvironments due to slow structural changes may provide a means for some virions to move and reach the port of entry, the underlying cervical mucosa.