Host Lipid Rafts Play a Major Role in Binding and Endocytosis of Influenza A Virus

• Main Authors: Dileep Kumar Verma, Dinesh Gupta, Sunil Kumar Lal
• Format: Article
• Language: English
• Published: MDPI AG 2018-11-01
• Series: Viruses
• Subjects: lipid raft; Cholesterol; Methyl-β-Cyclodextrin; Ganglioside GM1; Raft-dependent endocytosis
• Online Access: https://www.mdpi.com/1999-4915/10/11/650

Influenza still remains one of the most challenging diseases, posing a significant threat to public health. Host lipid rafts play a critical role in influenza A virus (IAV) assembly and budding, however, their role in polyvalent IAV host binding and endocytosis had remained elusive until now. In the present study, we observed co-localization of IAV with a lipid raft marker ganglioside, GM1, on the host surface. Further, we isolated the lipid raft micro-domains from IAV infected cells and detected IAV protein in the raft fraction. Finally, raft disruption using Methyl-β-Cyclodextrin revealed significant reduction in IAV host binding, suggesting utilization of host rafts for polyvalent binding on the host cell surface. In addition to this, cyclodextrin mediated inhibition of raft-dependent endocytosis showed significantly reduced IAV internalization. Interestingly, exposure of cells to cyclodextrin two hours post-IAV binding showed no such reduction in IAV entry, indicating use of raft-dependent endocytosis for host entry. In summary, this study demonstrates that host lipid rafts are selected by IAV as a host attachment factors for multivalent binding, and IAV utilizes these micro-domains to exploit raft-dependent endocytosis for host internalization, a virus entry route previously unknown for IAV.