Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses

Abstract

Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In this study, we analyzed the role of cholesterol on influenza A virus (IAV) and respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human airway cells with the agents did not decrease virus particle production. However, the released virions were less homogeneous in density and unstable. Addition of exogenous cholesterol to the released virions restored virus stability and infectivity. Collectively, these data indicate a critical role of cholesterol in maintaining IAV and RSV membrane structure that is essential for sustaining viral stability and infectivity.

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Cellular cholesterol abundance regulates potassium accumulation within endosomes and is an important determinant in bunyavirus entry

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Targeting host lipid flows: Exploring new antiviral and antibiotic strategies

“…Insertion of Gc is followed by accumulation of cholesterol and local membrane reorganisation (Guardado-Calvo et al, 2017).Depletion of cholesterol and consequent disruption of lipid rafts by methyl-β-cyclodextrin (MβCD) decreased the infectivity of Newcastle disease virus, WNV, HCV, and bovine parainfluenza virus, mainly through blocking virus entry into cells(Kapadia, Barth, Baumert, McKeating, & Chisari, 2007;Li, Yu, & Hou, 2017;Mackenzie, Khromykh, & Parton, 2007;Martin, Holguera, Sanchez-Felipe, Villar, & Munoz-Barroso, 2012). During influenza A and syncitial virus infections, a similar effect has been observed after treatment with gemfribrozil(Bajimaya, Frankl, Hayashi, & Takimoto, 2017) and with a natural elder fruit extract(Shahsavandi et al, 2017).…”