Specificity of human rhinovirus 2Apro is determined by combined spatial properties of four cleavage site residues

• DOI: 10.1099/vir.0.051201-0
• Publication Date: 2013-04-12T02:11:28Z
• Authors: David Neubauer; Martina Aumayr; Irene Gösler; Tim Skern
• Keywords: Cleavage (geology)

The 2A proteinase (2A(pro)) of human rhinoviruses cleaves the virally encoded polyprotein between C terminus VP1 and its own N terminus. Poor understanding 2A(pro) substrate specificity this enzyme has hampered progress in developing inhibitors that may serve as antiviral agents. We show here rhinovirus (HRV) 1A 2 (rhinoviruses from genetic group A) cannot self-process at HRV14 (a B rhinovirus) cleavage site. When amino acids site HRV2 (Ile-Ile-Thr-Thr-Ala*Gly-Pro-Ser-Asp) were singly or doubly replaced with corresponding residues (Asp-Ile-Lys-Ser-Tyr*Gly-Leu-Gly-Pro) positions P3 to P2', HRV1A took place WT levels. However, when three more substituted (e.g. P2, P1 P2'), vitro was essentially eliminated. Introduction full into a full-length clone transfection HeLa cells transcribed RNA did not give rise viable virus. In contrast, revertant viruses bearing cysteine position proline P2' obtained an inhibitory transfected. Reversions affecting found any vivo experiments. Modelling oligopeptide substrates onto structure revealed no appreciable differences respective binding sites, suggesting overall shape is important determining efficiency.