| First Author | Respondek D | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 3 | Pages | e0173259 |
| PubMed ID | 28278207 | Mgi Jnum | J:246836 |
| Mgi Id | MGI:5917220 | Doi | 10.1371/journal.pone.0173259 |
| Citation | Respondek D, et al. (2017) PA28 modulates antigen processing and viral replication during coxsackievirus B3 infection. PLoS One 12(3):e0173259 |
| abstractText | The function of the proteasome is modulated at the level of subunit expression and by association with its regulatory complexes. During coxsackievirus B3 (CVB3) myocarditis, IFN-induced formation of immunoproteasomes (ip) is known to be critical for regulating immune modulating molecules. The function of the IFN-gamma-inducible proteasome regulator subunits PA28 alpha and beta, however, in this context was unknown. During viral myocarditis, we found an increased abundance of PA28beta subunits in heart tissue. PA28alpha/beta exists in PA28-20S-PA28 and PA700-20S-PA28 hybrid proteasome complexes in cells both with either predominant ip and standard proteasome (sp) expression. Being in line with reduced proteasome activity in PA28alpha/beta-deficient cells, we observed increased levels of oxidized and poly-ubiquitinated proteins upon TLR3-activation in these cells. Moreover, PA28alpha/beta is capable to interfere directly with viral replication of CVB3 and facilitates the generation of CVB3-derived MHC class I epitopes by the proteasome. In contrast to a distinct function of PA28alpha/beta in vitro, gene ablation of PA28alpha/beta in mice being on a genetic background with resistance towards the development of severe infection had no significant impact on disease progression. Other than reported for the ip, in this host PA28alpha/beta is dispensable to meet the demand of increased peptide hydrolysis capacity by the proteasome during viral myocarditis. |
