Cholesterol dependence of Newcastle Disease Virus entry

Martín, Juan José; Holguera, Javier; Sánchez-Felipe, Lorena; Villar, Enrique; Muñoz-Barroso, Isabel

Lipid rafts are membrane microdomains enriched in cholesterol, sphingolipids, and glycolipids that have been implicated in many biological processes. Since cholesterol is known to play a key role in the entry of some other viruses, we investigated the role of cholesterol and lipid rafts in the host cell plasma membrane in Newcastle Disease Virus (NDV) entry. We used methyl-β-cyclodextrin (MβCD) to deplete cellular cholesterol and disrupt lipid rafts. Our results show that the removal of cellular cholesterol partially reduces viral binding, fusion and infectivity. MβCD had no effect on the expression of sialic acid containing molecule expression, the NDV receptors in the target cell. All the above-described effects were reversed by restoring cholesterol levels in the target cell membrane. The HN viral attachment protein partially localized to detergent-resistant membrane microdomains (DRMs) at 4 °C and then shifted to detergent-soluble fractions at 37 °C. These results indicate that cellular cholesterol may be required for optimal cell entry in NDV infection cycle.