MβCD inhibits SFTSV entry by disrupting lipid raft structure of the host cells

Antiviral Res. 2024 Nov:231:106004. doi: 10.1016/j.antiviral.2024.106004. Epub 2024 Sep 10.

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV), recently named as Dabie bandavirus, belongs to the family Phenuiviridae of the order Bunyavirales, is a newly-identified bunyavirus with a case fatality rate of up to 30%, posing a serious threat to public health. Lipid rafts on plasm membranes are important for the entry of enveloped viruses; however, the role of lipid rafts in bunyavirus entry remains unclear. In this study, we found that methyl-beta-cyclodextrin (MβCD), a drug that disrupts cholesterol in lipid rafts of cell membranes, inhibits SFTSV infection. Additionally, there is a back-complementary effect of SFTSV infection upon the addition of cholesterol. Moreover, the concentration of SFTSV particles in lipid rafts during entry directly indicated the role of lipid rafts as a gateway, whereas MβCD could inhibit SFTSV entry by affecting the structure of lipid rafts. In an in vivo study, MβCD also reduced the susceptibility of mice to SFTSV infection. Our results suggest that SFTSV can interact with Talin1 proteins on lipid rafts to enter host cells by endocytosis of lipid rafts and reveal the potential therapeutic value of MβCD for SFTSV infection.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Bunyaviridae Infections / virology
  • Cell Line
  • Chlorocebus aethiops
  • Cholesterol / metabolism
  • Endocytosis / drug effects
  • Humans
  • Membrane Microdomains* / drug effects
  • Membrane Microdomains* / metabolism
  • Mice
  • Phlebovirus* / drug effects
  • Phlebovirus* / physiology
  • Vero Cells
  • Virus Internalization* / drug effects
  • beta-Cyclodextrins* / pharmacology

Substances

  • methyl-beta-cyclodextrin
  • beta-Cyclodextrins
  • Cholesterol
  • Antiviral Agents