6533b7d9fe1ef96bd126c481
RESEARCH PRODUCT
Host Cell Calpains Can Cleave Structural Proteins from the Enterovirus Polyprotein
Vesa P. HytönenMira LaajalaJuha A. E. MäättäVarpu MarjomäkiMinna M. HankaniemiOlli H. Laitinensubject
0301 basic medicineProteasesentsyymitRNA virusviruksetvirusesPeptideCleavage (embryo)infektiotMass SpectrometryArticle03 medical and health sciencesViral ProteinsCapsidVirologyCleaveEnterovirus InfectionsAnimalsHumansCells CulturedGlycoproteinsPolyproteinschemistry.chemical_classification030102 biochemistry & molecular biologybiologyChemistryCalpainenterovirusvirus diseasesRNA virusCalpainbiochemical phenomena metabolism and nutritionbiology.organism_classificationAmino acidRatspolyproteinenterovirukset030104 developmental biologyInfectious DiseasesBiochemistryCapsidproteolytic processingProteolysisbiology.proteinCapsid ProteinsproteiinitPeptidescalpaindescription
Enteroviruses are small RNA viruses that cause diseases with various symptoms ranging from mild to severe. Enterovirus proteins are translated as a single polyprotein, which is cleaved by viral proteases to release capsid and nonstructural proteins. Here, we show that also cellular calpains have a potential role in the processing of the enteroviral polyprotein. Using purified calpains 1 and 2 in an in vitro assay, we show that addition of calpains leads to an increase in the release of VP1 and VP3 capsid proteins from P1 of enterovirus B species, detected by western blotting. This was prevented with a calpain inhibitor and was dependent on optimal calcium concentration, especially for calpain 2. In addition, calpain cleavage at the VP3-VP1 interface was supported by a competition assay using a peptide containing the VP3-VP1 cleavage site. Moreover, a mass spectrometry analysis showed that calpains can cleave this same peptide at the VP3-VP1 interface, the cutting site being two amino acids aside from 3C&rsquo
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-11-28 |