Role of non-raft cholesterol in lymphocytic choriomeningitis virus infection via α-dystroglycan

Dystroglycan (DG) is an extracellular matrix receptor necessary for the development of metazoans from flies to humans and is also an entry route for various pathogens. Lymphocytic choriomeningitis virus (LCMV), a member of the family Arenaviridae, infects by binding to alpha-DG. Here, the role of cholesterol lipid rafts in infection by LCMV via alpha-DG was investigated. The cholesterol-sequestering drugs methyl-beta-cyclodextrin (M beta CD), filipin and nystatin inhibited the infectivity of LCMV selectively, but did not affect infection by vesicular stomatitis virus. Cholesterol loading after depletion with M beta CD restored infectivity to control levels. DG was not found in lipid rafts identified with the raft marker ganglioside GM1. Treatment with M beta CD, however, enhanced the solubility of DG. This may reflect the association of DG with cholesterol outside lipid rafts and suggests that association of DG with non-raft cholesterol is critical for infection by LCMV through alpha-DG.