Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer
Herpesviruses cause severe diseases particularly in immunocompromised patients. Both genome packaging and release from the capsid require a unique portal channel occupying one of the 12 capsid vertices. Here, we report the 2.6 Å crystal structure of the pentameric pORF19 of the γ-herpesvirus Kaposi’...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-11-01
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| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568140/?tool=EBI |
| _version_ | 1818931302791905280 |
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| author | Peter Naniima Eleonora Naimo Sandra Koch Ute Curth Khaled R. Alkharsah Luisa J. Ströh Anne Binz Jan-Marc Beneke Benjamin Vollmer Heike Böning Eva Maria Borst Prashant Desai Jens Bohne Martin Messerle Rudolf Bauerfeind Pierre Legrand Beate Sodeik Thomas F. Schulz Thomas Krey |
| author_facet | Peter Naniima Eleonora Naimo Sandra Koch Ute Curth Khaled R. Alkharsah Luisa J. Ströh Anne Binz Jan-Marc Beneke Benjamin Vollmer Heike Böning Eva Maria Borst Prashant Desai Jens Bohne Martin Messerle Rudolf Bauerfeind Pierre Legrand Beate Sodeik Thomas F. Schulz Thomas Krey |
| author_sort | Peter Naniima |
| collection | DOAJ |
| description | Herpesviruses cause severe diseases particularly in immunocompromised patients. Both genome packaging and release from the capsid require a unique portal channel occupying one of the 12 capsid vertices. Here, we report the 2.6 Å crystal structure of the pentameric pORF19 of the γ-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV) resembling the portal cap that seals this portal channel. We also present the structure of its β-herpesviral ortholog, revealing a striking structural similarity to its α- and γ-herpesviral counterparts despite apparent differences in capsid association. We demonstrate pORF19 pentamer formation in solution and provide insights into how pentamerization is triggered in infected cells. Mutagenesis in its lateral interfaces blocked pORF19 pentamerization and severely affected KSHV capsid assembly and production of infectious progeny. Our results pave the way to better understand the role of pORF19 in capsid assembly and identify a potential novel drug target for the treatment of herpesvirus-induced diseases. In herpesviruses, genome packaging and release from the capsid require a unique portal channel. Here, the authors have resolved the crystal structure of a pentameric KSHV pORF19 assembly and find that it resembles the herpesviral portal cap and provides insights how the viral genome is retained within the capsid. |
| first_indexed | 2024-12-20T04:14:26Z |
| format | Article |
| id | doaj.art-5baa5853f4194387a43957495e2d295d |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-20T04:14:26Z |
| publishDate | 2021-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-5baa5853f4194387a43957495e2d295d2022-12-21T19:53:49ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-11-011911Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamerPeter NaniimaEleonora NaimoSandra KochUte CurthKhaled R. AlkharsahLuisa J. StröhAnne BinzJan-Marc BenekeBenjamin VollmerHeike BöningEva Maria BorstPrashant DesaiJens BohneMartin MesserleRudolf BauerfeindPierre LegrandBeate SodeikThomas F. SchulzThomas KreyHerpesviruses cause severe diseases particularly in immunocompromised patients. Both genome packaging and release from the capsid require a unique portal channel occupying one of the 12 capsid vertices. Here, we report the 2.6 Å crystal structure of the pentameric pORF19 of the γ-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV) resembling the portal cap that seals this portal channel. We also present the structure of its β-herpesviral ortholog, revealing a striking structural similarity to its α- and γ-herpesviral counterparts despite apparent differences in capsid association. We demonstrate pORF19 pentamer formation in solution and provide insights into how pentamerization is triggered in infected cells. Mutagenesis in its lateral interfaces blocked pORF19 pentamerization and severely affected KSHV capsid assembly and production of infectious progeny. Our results pave the way to better understand the role of pORF19 in capsid assembly and identify a potential novel drug target for the treatment of herpesvirus-induced diseases. In herpesviruses, genome packaging and release from the capsid require a unique portal channel. Here, the authors have resolved the crystal structure of a pentameric KSHV pORF19 assembly and find that it resembles the herpesviral portal cap and provides insights how the viral genome is retained within the capsid.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568140/?tool=EBI |
| spellingShingle | Peter Naniima Eleonora Naimo Sandra Koch Ute Curth Khaled R. Alkharsah Luisa J. Ströh Anne Binz Jan-Marc Beneke Benjamin Vollmer Heike Böning Eva Maria Borst Prashant Desai Jens Bohne Martin Messerle Rudolf Bauerfeind Pierre Legrand Beate Sodeik Thomas F. Schulz Thomas Krey Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer PLoS Biology |
| title | Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer |
| title_full | Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer |
| title_fullStr | Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer |
| title_full_unstemmed | Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer |
| title_short | Assembly of infectious Kaposi’s sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer |
| title_sort | assembly of infectious kaposi s sarcoma associated herpesvirus progeny requires formation of a porf19 pentamer |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568140/?tool=EBI |
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