The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism

Proc Natl Acad Sci U S A. 2021 Mar 16;118(11):e2019251118. doi: 10.1073/pnas.2019251118.


The mosquito protein AEG12 is up-regulated in response to blood meals and flavivirus infection though its function remained elusive. Here, we determine the three-dimensional structure of AEG12 and describe the binding specificity of acyl-chain ligands within its large central hydrophobic cavity. We show that AEG12 displays hemolytic and cytolytic activity by selectively delivering unsaturated fatty acid cargoes into phosphatidylcholine-rich lipid bilayers. This property of AEG12 also enables it to inhibit replication of enveloped viruses such as Dengue and Zika viruses at low micromolar concentrations. Weaker inhibition was observed against more distantly related coronaviruses and lentivirus, while no inhibition was observed against the nonenveloped virus adeno-associated virus. Together, our results uncover the mechanistic understanding of AEG12 function and provide the necessary implications for its use as a broad-spectrum therapeutic against cellular and viral targets.

Keywords: antiviral; cytolysis; insect digestion; insect immune response; membrane disruption.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism*
  • Antiviral Agents / pharmacology
  • Cell Line
  • Cell Membrane / metabolism
  • Culicidae
  • Erythrocytes / drug effects
  • Fatty Acids, Unsaturated / metabolism
  • Hemolytic Agents / chemistry
  • Hemolytic Agents / metabolism*
  • Hemolytic Agents / pharmacology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Insect Proteins / chemistry
  • Insect Proteins / metabolism*
  • Insect Proteins / pharmacology
  • Ligands
  • Lipids* / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Viral Envelope / metabolism
  • Viruses / drug effects
  • Viruses / metabolism


  • Antiviral Agents
  • Fatty Acids, Unsaturated
  • Hemolytic Agents
  • Insect Proteins
  • Ligands
  • Lipids