Publication details
The Structure of Human Parechovirus 1 Reveals an Association of the RNA Genome with the Capsid
| Authors | |
|---|---|
| Year of publication | 2016 |
| Type | Article in Periodical |
| Magazine / Source | JOURNAL OF VIROLOGY |
| MU Faculty or unit | |
| Citation | |
| Web | http://jvi.asm.org/content/90/3/1377 |
| Doi | http://dx.doi.org/10.1128/JVI.02346-15 |
| Field | Microbiology, virology |
| Keywords | ELECTRON-DENSITY; HUMAN RHINOVIRUS-14; PICORNAVIRUS GROUP; COXSACKIEVIRUS A9; CRYSTAL-STRUCTURE; VP1 PROTEIN; NMR SYSTEM; ENTEROVIRUS; RECEPTOR; INFECTIONS |
| Description | Parechoviruses are human pathogens that cause diseases ranging from gastrointestinal disorders to encephalitis. Unlike those of most picornaviruses, parechovirus capsids are composed of only three subunits: VP0, VP1, and VP3. Here, we present the structure of a human parechovirus 1 (HPeV-1) virion determined to a resolution of 3.1 angstrom. We found that interactions among pentamers in the HPeV-1 capsid are mediated by the N termini of VP0s, which correspond to the capsid protein VP4 and the N-terminal part of the capsid protein VP2 of other picornaviruses. In order to facilitate delivery of the virus genome into the cytoplasm, the N termini of VP0s have to be released from contacts between pentamers and exposed at the particle surface, resulting in capsid disruption. A hydrophobic pocket, which can be targeted by capsid-binding antiviral compounds in many other picornaviruses, is not present in HPeV-1. However, we found that interactions between the HPeV-1 single-stranded RNA genome and subunits VP1 and VP3 in the virion impose a partial icosahedral ordering on the genome. The residues involved in RNA binding are conserved among all parechoviruses, suggesting a putative role of the genome in virion stability or assembly. Therefore, putative small molecules that could disrupt HPeV RNA-capsid protein interactions could be developed into antiviral inhibitors. |