Influenza virus causes infected cells to generate large numbers of lipid droplets. Because the virus envelope contains substantial cholesterol, we applied atorvastatin (ATV) to Madin-Darby Canine Kidney cells before infecting them. Five micromolars ATV, within physiologic range, strongly (>95%) inhibits reproduction of influenza A as measured by PCR of viral RNA, plaque assay for viable virus, and production of virus nucleoprotein (NP). Inhibition of any of the following can suppress formation of lipid droplets (>-50%) but does not interfere with the production of NP: endoplasmic reticulum stress, autophagy, or production of reactive oxygen substances (ROS). We conclude that, regardless of whether this widely used statin, which is generally considered to be safe, can prevent infection or minimize its severity, inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway to protect against infection by influenza virus or to mitigate its severity warrants further exploration.-Episcopio, D., Aminov, S., Benjamin, S., Germain, G., Datan, E., Landazuri, J., Lockshin, R. A., Zakeri, Z. Atorvastatin restricts the ability of influenza virus to generate lipid droplets and severely suppresses the replication of the virus.
Keywords: ER stress; autophagy; cholesterol; statin; viral infection.