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

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.
Authors	Alexander C Y Foo, Peter M Thompson, Shih-Heng Chen, Ramesh Jadi, Brianna Lupo, Eugene F DeRose, Simrat Arora, Victoria C Placentra, Lakshmanane Premkumar, Lalith Perera, Lars C Pedersen, Negin Martin, Geoffrey A Mueller
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 118 Issue 11 (03 16 2021) ISSN: 1091-6490 [Electronic] United States
PMID	33688047 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References	Antiviral Agents Fatty Acids, Unsaturated Hemolytic Agents Insect Proteins Ligands Lipids
Topics	Animals Antiviral Agents (chemistry, metabolism, pharmacology) Cell Line Cell Membrane (metabolism) Culicidae Erythrocytes (drug effects) Fatty Acids, Unsaturated (metabolism) Hemolytic Agents (chemistry, metabolism, pharmacology) Humans Hydrophobic and Hydrophilic Interactions Insect Proteins (chemistry, metabolism, pharmacology) Ligands Lipids (chemistry) Protein Binding Protein Structure, Tertiary Viral Envelope (metabolism) Viruses (drug effects, metabolism)

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