title: Modeling of the human rhinovirus C capsid suggests a novel topography with insights on receptor preference and immunogenicity.
abstract: Features of human rhinovirus (RV)-C virions that allow them to use novel cell receptors and evade immune responses are unknown. Unlike the RV-A+B, these isolates cannot be propagated in typical culture systems or grown for structure studies. Comparative sequencing, I-TASSER, MODELLER, ROBETTA, and refined alignment techniques led to a structural approximation for C15 virions, based on the extensive, resolved RV-A+B datasets. The model predicts that all RV-C VP1 proteins are shorter by 21 residues relative to the RV-A, and 35 residues relative to the RV-B, effectively shaving the RV 5-fold plateau from the particle. There are major alterations in VP1 neutralizing epitopes and the structural determinants for ICAM-1 and LDLR receptors. The VP2 and VP3 elements are similar among all RV, but the loss of sequence "words" contributing Nim1ab has increased the apparent selective pressure among the RV-C to fix mutations elsewhere in the VP1, creating a possible compensatory epitope.
authors: Institute for Molecular Virology, University of Wisconsin, Madison, USA.
authors: Holly A
authors: HA
authors: Basta
authors: Jean-Yves
authors: JY
authors: Sgro
authors: Ann C
authors: AC
authors: Palmenberg
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010850:Picornaviridae Infections / Q000276:immunology / Q000821:virology*; D011973:Receptors, LDL / Q000276:immunology; D011991:Receptors, Virus / Q000276:immunology*; D012229:Rhinovirus / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: C573412:LDLR protein, human; D011973:Receptors, LDL; D011991:Receptors, Virus; D014764:Viral Proteins; C074995:viral protein 1, rhinovirus; D018799:Intercellular Adhesion Molecule-1
keywords: Capsid structure; I-Tasser; Immunogenicity; Model; Receptor binding; Rhinovirus; Rhinovirus C