Poxviruses Encode a Reticulon-Like Protein that Promotes Membrane Curvature

• Predicted structure of poxvirus A17 protein resembles ER tubule-forming reticulons
• Purified A17 protein interacts with lipids to form 25 nm vesicles and tubules
• Overexpression of A17 transforms the ER into a highly curved, tightly packed network
• A17 contributes to curvature during viral membrane biogenesis from the ER

SummaryPoxviruses are enveloped DNA viruses that replicate within the cytoplasm. The first viral structures are crescents and spherical particles, with a lipoprotein membrane bilayer, that are thought to be derived from the ER. We determined that A17, a conserved viral transmembrane protein essential for crescent formation, forms homo-oligomers and shares topological features with cellular reticulon-like proteins. The latter cell proteins promote membrane curvature and contribute to the tubular structure of the ER. When the purified A17 protein was incorporated into liposomes, 25 nm diameter vesicles and tubules formed at low and high A17 concentrations, respectively. In addition, intracellular expression of A17 in the absence of other viral structural proteins transformed the ER into aggregated three-dimensional (3D) tubular networks. We suggest that A17 is a viral reticulon-like protein that contributes to curvature during biogenesis of the poxvirus membrane.

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