Structural changes and aggregation of human influenza virus.

Abstract

The pH-induced change in the structure and aggregation state of the PR-8 and X-31 strains of intact human influenza virus has been studied in vitro. Reducing the pH from 7.4 to 5.0 produces a large increase in the intensity of light scattered to low angles. A modest increase in the polydispersity parameter from cumulants fits to the dynamic light scattering correlograms accompanies the increase, as does a change in how that parameter varies with scattering angle. These trends imply that the virus particles are not uniform, even at pH 7.4, and tend to aggregate as pH is reduced. The scattering profiles (angular dependence of intensity) never match those of isolated, spherical particles of uniform size, but the deviations from that simple model remain modest at pH 7.4. At pH 5.0, scattering profiles calculated for aggregates of uniformly sized spheres come much closer to matching the experimental data than those computed for isolated particles. Although these observations indicate that acid-induced aggregation develops over a period of minutes to hours after acidification, a nearly instantaneous increase in hydrodynamic size is the first response of intact virus particles to lower pH.