The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses.
The replication of many RNA viruses involves the translation of polyproteins, whose processing by endopeptidases is a critical step for the release of functional subunits. P1 is the first protease encoded in plant potyvirus genomes; once activated by an as-yet-unknown host factor, it acts in cis on...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-03-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3946448?pdf=render |
| _version_ | 1818827774549295104 |
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| author | Fabio Pasin Carmen Simón-Mateo Juan Antonio García |
| author_facet | Fabio Pasin Carmen Simón-Mateo Juan Antonio García |
| author_sort | Fabio Pasin |
| collection | DOAJ |
| description | The replication of many RNA viruses involves the translation of polyproteins, whose processing by endopeptidases is a critical step for the release of functional subunits. P1 is the first protease encoded in plant potyvirus genomes; once activated by an as-yet-unknown host factor, it acts in cis on its own C-terminal end, hydrolyzing the P1-HCPro junction. Earlier research suggests that P1 cooperates with HCPro to inhibit host RNA silencing defenses. Using Plum pox virus as a model, we show that although P1 does not have a major direct role in RNA silencing suppression, it can indeed modulate HCPro function by its self-cleavage activity. To study P1 protease regulation, we used bioinformatic analysis and in vitro activity experiments to map the core C-terminal catalytic domain. We present evidence that the hypervariable region that precedes the protease domain is predicted as intrinsically disordered, and that it behaves as a negative regulator of P1 proteolytic activity in in vitro cleavage assays. In viral infections, removal of the P1 protease antagonistic regulator is associated with greater symptom severity, induction of salicylate-dependent pathogenesis-related proteins, and reduced viral loads. We suggest that fine modulation of a viral protease activity has evolved to keep viral amplification below host-detrimental levels, and thus to maintain higher long-term replicative capacity. |
| first_indexed | 2024-12-19T00:48:54Z |
| format | Article |
| id | doaj.art-9b070ffee6544c7aafc5e652ed01f8c9 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-19T00:48:54Z |
| publishDate | 2014-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-9b070ffee6544c7aafc5e652ed01f8c92022-12-21T20:44:09ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-03-01103e100398510.1371/journal.ppat.1003985The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses.Fabio PasinCarmen Simón-MateoJuan Antonio GarcíaThe replication of many RNA viruses involves the translation of polyproteins, whose processing by endopeptidases is a critical step for the release of functional subunits. P1 is the first protease encoded in plant potyvirus genomes; once activated by an as-yet-unknown host factor, it acts in cis on its own C-terminal end, hydrolyzing the P1-HCPro junction. Earlier research suggests that P1 cooperates with HCPro to inhibit host RNA silencing defenses. Using Plum pox virus as a model, we show that although P1 does not have a major direct role in RNA silencing suppression, it can indeed modulate HCPro function by its self-cleavage activity. To study P1 protease regulation, we used bioinformatic analysis and in vitro activity experiments to map the core C-terminal catalytic domain. We present evidence that the hypervariable region that precedes the protease domain is predicted as intrinsically disordered, and that it behaves as a negative regulator of P1 proteolytic activity in in vitro cleavage assays. In viral infections, removal of the P1 protease antagonistic regulator is associated with greater symptom severity, induction of salicylate-dependent pathogenesis-related proteins, and reduced viral loads. We suggest that fine modulation of a viral protease activity has evolved to keep viral amplification below host-detrimental levels, and thus to maintain higher long-term replicative capacity.http://europepmc.org/articles/PMC3946448?pdf=render |
| spellingShingle | Fabio Pasin Carmen Simón-Mateo Juan Antonio García The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses. PLoS Pathogens |
| title | The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses. |
| title_full | The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses. |
| title_fullStr | The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses. |
| title_full_unstemmed | The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses. |
| title_short | The hypervariable amino-terminus of P1 protease modulates potyviral replication and host defense responses. |
| title_sort | hypervariable amino terminus of p1 protease modulates potyviral replication and host defense responses |
| url | http://europepmc.org/articles/PMC3946448?pdf=render |
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