title: Crystal structure of a nematode-infecting virus.
abstract: Orsay, the first virus discovered to naturally infect Caenorhabditis elegans or any nematode, has a bipartite, positive-sense RNA genome. Sequence analyses show that Orsay is related to nodaviruses, but molecular characterizations of Orsay reveal several unique features, such as the expression of a capsid-δ fusion protein and the use of an ATG-independent mechanism for translation initiation. Here we report the crystal structure of an Orsay virus-like particle assembled from recombinant capsid protein (CP). Orsay capsid has a T = 3 icosahedral symmetry with 60 trimeric surface spikes. Each CP can be divided into three regions: an N-terminal arm that forms an extended protein interaction network at the capsid interior, an S domain with a jelly-roll, β-barrel fold forming the continuous capsid, and a P domain that forms surface spike projections. The structure of the Orsay S domain is best aligned to T = 3 plant RNA viruses but exhibits substantial differences compared with the insect-infecting alphanodaviruses, which also lack the P domain in their CPs. The Orsay P domain is remotely related to the P1 domain in calicivirus and hepatitis E virus, suggesting a possible evolutionary relationship. Removing the N-terminal arm produced a slightly expanded capsid with fewer nucleic acids packaged, suggesting that the arm is important for capsid stability and genome packaging. Because C. elegans-Orsay serves as a highly tractable model for studying viral pathogenesis, our results should provide a valuable structural framework for further studies of Orsay replication and infection.
authors.affiliation: Department of BioSciences, Rice University, Houston, TX 77005;
authors.forename: Yusong R
authors.initials: YR
authors.lastname: Guo
authors.affiliation: Graduate Program in Structural and Computational Biology and Molecular Biophysics and Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030; and.
authors.forename: Corey F
authors.initials: CF
authors.lastname: Hryc
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030; and.
authors.forename: Joanita
authors.initials: J
authors.lastname: Jakana
authors.affiliation: Departments of Molecular Microbiology and Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Departments of Molecular Microbiology and Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.affiliation: Graduate Program in Structural and Computational Biology and Molecular Biophysics and Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030; and.
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
authors.affiliation: Department of BioSciences, Rice University, Houston, TX 77005;
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of BioSciences, Rice University, Houston, TX 77005; ytao@rice.edu.
authors.forename: Yizhi J
authors.initials: YJ
authors.lastname: Tao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000821:virology*; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D030381:Nodaviridae / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D014774:Virulence
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral
keywords: crystallography; microscopy; virology