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Published on: May 29, 2016
Structural changes and aggregation of human influenza virus
Jason N Campbell1, Richard M Epand, Paul S Russo
1Department of Chemistry, Louisiana State University, Baton Rouge 70803-1804, USA.
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.
Insights
Lowering pH causes intact human influenza virus particles to rapidly increase in size and aggregate. This pH-induced aggregation is a key factor in understanding influenza virus behavior in different environments.
Area of Science:
- Virology
- Biophysics
- Materials Science
Background:
- Human influenza virus (PR-8 and X-31 strains) structural changes were investigated.
- Understanding virus behavior under varying pH conditions is crucial for virology and drug development.
Purpose of the Study:
- To investigate the in vitro pH-induced structural and aggregation changes in intact human influenza virus particles.
- To characterize the dynamic light scattering changes associated with pH reduction.
Main Methods:
- Dynamic light scattering (DLS) was used to study virus particle size and aggregation.
- Scattering profiles were analyzed at different pH levels (7.4 and 5.0).
Main Results:
- Reducing pH from 7.4 to 5.0 caused a significant increase in light scattering intensity.
- Virus particles showed increased polydispersity and aggregation at lower pH.
- Scattering profiles at pH 5.0 closely matched models of aggregated spheres, not isolated particles.
Conclusions:
- Intact influenza virus particles exhibit an instantaneous increase in hydrodynamic size upon acidification.
- Acidification induces virus particle aggregation over minutes to hours.
- Virus particles are non-uniform and prone to aggregation at reduced pH.
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