Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance.
Modified-live herpesvirus vaccines are widely used in humans and animals, but field strains can emerge that have a higher virulence and break vaccinal protection. Since the introduction of the first vaccine in the 1970s, Marek's disease virus overcame the vaccine barrier by the acquisition of n...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009104 |
| _version_ | 1818581352943976448 |
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| author | Andelé M Conradie Luca D Bertzbach Jakob Trimpert Joseph N Patria Shiro Murata Mark S Parcells Benedikt B Kaufer |
| author_facet | Andelé M Conradie Luca D Bertzbach Jakob Trimpert Joseph N Patria Shiro Murata Mark S Parcells Benedikt B Kaufer |
| author_sort | Andelé M Conradie |
| collection | DOAJ |
| description | Modified-live herpesvirus vaccines are widely used in humans and animals, but field strains can emerge that have a higher virulence and break vaccinal protection. Since the introduction of the first vaccine in the 1970s, Marek's disease virus overcame the vaccine barrier by the acquisition of numerous genomic mutations. However, the evolutionary adaptations in the herpesvirus genome responsible for the vaccine breaks have remained elusive. Here, we demonstrate that point mutations in the multifunctional meq gene acquired during evolution can significantly alter virulence. Defined mutations found in highly virulent strains also allowed the virus to overcome innate cellular responses and vaccinal protection. Concomitantly, the adaptations in meq enhanced virus shedding into the environment, likely providing a selective advantage for the virus. Our study provides the first experimental evidence that few point mutations in a single herpesviral gene result in drastically increased virulence, enhanced shedding, and escape from vaccinal protection. |
| first_indexed | 2024-12-16T07:32:08Z |
| format | Article |
| id | doaj.art-a5a6bd3966704d7f81b604ef039ab1c2 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T07:32:08Z |
| publishDate | 2020-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a5a6bd3966704d7f81b604ef039ab1c22022-12-21T22:39:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-12-011612e100910410.1371/journal.ppat.1009104Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance.Andelé M ConradieLuca D BertzbachJakob TrimpertJoseph N PatriaShiro MurataMark S ParcellsBenedikt B KauferModified-live herpesvirus vaccines are widely used in humans and animals, but field strains can emerge that have a higher virulence and break vaccinal protection. Since the introduction of the first vaccine in the 1970s, Marek's disease virus overcame the vaccine barrier by the acquisition of numerous genomic mutations. However, the evolutionary adaptations in the herpesvirus genome responsible for the vaccine breaks have remained elusive. Here, we demonstrate that point mutations in the multifunctional meq gene acquired during evolution can significantly alter virulence. Defined mutations found in highly virulent strains also allowed the virus to overcome innate cellular responses and vaccinal protection. Concomitantly, the adaptations in meq enhanced virus shedding into the environment, likely providing a selective advantage for the virus. Our study provides the first experimental evidence that few point mutations in a single herpesviral gene result in drastically increased virulence, enhanced shedding, and escape from vaccinal protection.https://doi.org/10.1371/journal.ppat.1009104 |
| spellingShingle | Andelé M Conradie Luca D Bertzbach Jakob Trimpert Joseph N Patria Shiro Murata Mark S Parcells Benedikt B Kaufer Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance. PLoS Pathogens |
| title | Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance. |
| title_full | Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance. |
| title_fullStr | Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance. |
| title_full_unstemmed | Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance. |
| title_short | Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance. |
| title_sort | distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance |
| url | https://doi.org/10.1371/journal.ppat.1009104 |
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