Publikationsdatenbank

Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Conradie, Andelé M. (WE 5)

Bertzbach, Luca D. (WE 5)

Trimpert, Jakob (WE 5)

Patria, Joseph N.

Murata, Shiro

Parcells, Mark S.

Kaufer, Benedikt B. (WE 5)

Quelle

PLoS pathogens

Bandzählung: 16

Heftzählung: 12

Seiten: e1009104

ISSN: 1553-7374

Sprache

Englisch

Verweise

URL (Volltext): https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009104

DOI: 10.1371/journal.ppat.1009104

Pubmed: 33306739

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.