1. The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism
- Author
-
Eugene F. DeRose, Simrat Arora, Peter M. Thompson, Lars C. Pedersen, Brianna Lupo, Negin P. Martin, Victoria C. Placentra, Geoffrey A. Mueller, Lalith Perera, Alexander C. Y. Foo, Shih Heng Chen, Ramesh Jadi, and Lakshmanane Premkumar
- Subjects
0301 basic medicine ,Erythrocytes ,viruses ,Ligands ,Antiviral Agents ,Virus ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Viral envelope ,Animals ,Humans ,Lipid bilayer ,Unsaturated fatty acid ,Binding selectivity ,Multidisciplinary ,biology ,Chemistry ,Hemolytic Agents ,Cell Membrane ,Biological Sciences ,biology.organism_classification ,Lipids ,Cell biology ,Protein Structure, Tertiary ,Flavivirus ,030104 developmental biology ,Culicidae ,Viral Envelope ,Lentivirus ,Viruses ,Fatty Acids, Unsaturated ,Insect Proteins ,Hydrophobic and Hydrophilic Interactions ,030217 neurology & neurosurgery ,Function (biology) ,Protein Binding - Abstract
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.
- Published
- 2021