Shear-Reversible Clusters of HIV-1 in Solution: Stabilized by Antibodies, Dispersed by Mucin

The behavior of HIV-1 in culture media was tracked with Dynamic Light Scattering (DLS) and complementary atomic force microscopy (AFM) imaging in the presence of lectins, anti-gp120 Antibodies (Abs), mannosidase, and mucin. After excluding the serum contribution to culture media from extracted DLS data, it is observed that there are clusters/ aggregates of about 400-700nm HIV-1 in solutions. The clusters were sheared into single virus particles by filtration but re-clustered back over a short time. It is known that HIV-1 mutates rapidly and is protected by glycan shields of mannose sugars that have challenged the broadly neutralizing of the virus by Abs. In other studies, mannose residues have been reported to be self-adhesive, but it is not known if these mannose adhesions drive HIV-1 to be aggregated in solution, further confounding Ab neutralization. Mannosidase treatment reduced clustering, suggesting the mannose glycan shield is involved in the cluster formation. Mucin molecules (porcine gastric mucin) effectively dispersed HIV-1 clusters, even those stabilized by Abs. It is well known that mucin reduces HIV virulence, but the mechanism has not been clarified. Our findings suggest that mucin reduces HIV-1 virulence by dispersing its clusters, as opposed to the current perspective that mucin aggregates HIV-1.