Yizhi Jane Tao, Ph.D

Professor of Biochemistry
Dept of BioSciences
Rice University

Title: The Tale (Tail) of the Nematode Virus Orsay.

Abstract:

Since 2012, our laboratory has been closely studying a newly discovered virus called Orsay, the only virus known to naturally infect the model nematode C. elegans. Orsay infection occurs in the worm intestine, which consists of 20 large epithelial cells that resemble human intestinal epithelial cells. Therefore, the C. elegans-Orsay system provides an excellent model to study natural host-virus interactions in a live, intact animal. The Orsay virus and its related nematode viruses have a positive-sense RNA genome that encode three proteins: capsid protein (CP), RNA-dependent RNA polymerase (RdRP), and a novel δ protein that shares no homology with any other proteins. Recently we determined the Orsay capsid structure, which shows a structural fold related to fish-infecting betanodaviruses, but distinct from the insect-infecting alphanodaviruses. We further demonstrated that the Orsay δ protein forms a ~420-Å long, pentameric fiber with an α-helical coiled coil at the N-terminus, a β-stranded shaft in the middle, and a globular head domain at the C-terminal end. In addition to a free protein, the δ sequence could also be expressed as a CP-δ fusion protein. CP-δ is incorporated into Orsay capsids, producing long fibers projecting from the capsid surface. Multiple lines of evidence from our biochemistry and cell biology studies established that CP-δ functions as a cell receptor binding protein, whereas the free δ interacts with the host cell cytoskeleton to facilitate nonlytic virus release at the apical side of the worm intestine. In collaboration with Dr. Weiwei Zhong’s lab at Rice University, a genome-wide RNAi screen was performed, and a total of 103 antiviral genes were identified. Initial pathway mapping suggested that there are a least three groups of genes with distinct functions in innate antiviral defense.