Modulating cholesterol-rich lipid rafts to disrupt influenza A virus infection

Abstract

Influenza A virus (IAV) is widely disseminated across different species and can cause recurrent epidemics and severe pandemics in humans. During infection, IAV attaches to receptors that are predominantly located in cell membrane regions known as lipid rafts, which are highly enriched in cholesterol and sphingolipids. Following IAV entry into the host cell, uncoating, transcription, and replication of the viral genome occur, after which newly synthesized viral proteins and genomes are delivered to lipid rafts for assembly prior to viral budding from the cell. Moreover, during budding, IAV acquires an envelope with embedded cholesterol from the host cell membrane, and it is known that decreased cholesterol levels on IAV virions reduce infectivity. Statins are commonly used to inhibit cholesterol synthesis for preventing cardiovascular diseases, and several studies have investigated whether such inhibition can block IAV infection and propagation, as well as modulate the host immune response to IAV. Taken together, current research suggests that there may be a role for statins in countering IAV infections and modulating the host immune response to prevent or mitigate cytokine storms, and further investigation into this is warranted.

Association between Statins Administration and Influenza Susceptibility: A Systematic Review and Meta-Analysis of Longitudinal Studies

“…Mechanically, in addition to their potential anti-inflammatory effects, previous studies have demonstrated that statins could play multiple roles in the regulation of virus susceptibility. Statins can reduce cholesterol availability, disrupt lipid raft composition, alter membrane receptor assembly, and thus limit virus fusion and entry into host cells [ 46 ]. One study also demonstrated that statins reduced the replication of influenza H1N1 by blocking RhoA and LC3 lipidation localization and inducing actin filaments condensation [ 47 ].…”

Novel Transmission Electron Microscopic Method to Quantify Protein Clustering on the Cell Surface

“…The lipid bilayer provides the membrane with fluidity and elasticity. Studying lipid rafts present on cell surface proteins can provide detailed information on their functionality, e.g., T‐cell signaling, treatment of viral infection, receptor‐mediated channel activity, and therapeutic targets for cancer (Bobkov & Semenova, 2022; Carletti et al., 2017; Codini et al., 2021; Gold & Reth, 2019; Li et al., 2022; Magee et al., 2002; Nagy et al., 2001).…”

Inducing the Localization of HSP70 to Lipid Rafts by Borna Disease Virus 1 Promotes Its Invasion and Host Cells Apoptosis

“…While serving as a platform for cell communication, they increase the vulnerability of cells to pathogen invasion (19). Studies have shown that LR are crucial for many viruses to invade cells, such as Hepatitis C virus (20), Zika virus (21), and In uenza A virus (IAV) (22). In fact, the LR and its related signal molecules have recently become important targets and are rapidly being used to develop antiviral drugs.…”