FN Archimer Export Format PT J TI Structural variation turnovers and defective genomes: key drivers for the in vitro evolution of the large double-stranded DNA koi herpesvirus (KHV) BT AF Fuandila, Nurul Novelia Gosselin-Grenet, Anne-Sophie Tilak, Marie-Ka Bergmann, Sven M Escoubas, Jean-Michel Klafack, Sandro Lusiastuti, Angela Mariana Yuhana, Munti Fiston-Lavier, Anna-Sophie Avarre, Jean-Christophe Cherif, Emira AS 1:1;2:2;3:1;4:3;5:4;6:5;7:6;8:7;9:8;10:1;11:1; FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;10:;11:; C1 ISEM,UnivMontpellier, CNRS, IRD,Montpellier, France DGIMI,UnivMontpellier, INRAE,Montpellier, France Institute of Infectology, Friedrich-Loeffer-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany IHPE, Univ Montpellier, CNRS, Ifremer, UPVD, Montpellier, France Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffer-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany Fish Health Laboratory, Research Institute for Freshwater Aquaculture and Fisheries Extension, Bogor, Indonesia Faculty of Fisheries and Marine Sciences, Bogor Agricultural University, Indonesia Institut Universitaire de France (IUF), Paris, France C2 UNIV MONTPELLIER, FRANCE UNIV MONTPELLIER, FRANCE FRIEDRICH LOEFFER INST, GERMANY UNIV MONTPELLIER, FRANCE FRIEDRICH LOEFFER INST, GERMANY RIFAFE, INDONESIA UNIV AGRI BOGOR, INDONESIA INST UNIV FRANCE, FRANCE UM IHPE IN DOAJ TC 0 UR https://archimer.ifremer.fr/doc/00788/89971/95490.pdf LA English DT Article AB Structural variations (SVs) constitute a significant source of genetic variability in virus genomes. Yet knowledge about SV variability and contribution to the evolutionary process in large double-stranded (ds)DNA viruses is limited. Cyprinid herpesvirus 3 (CyHV-3), also commonly known as koi herpesvirus (KHV), has the largest dsDNA genome within herpesviruses. This virus has become one of the biggest threats to common carp and koi farming, resulting in high morbidity and mortalities of fishes, serious environmental damage, and severe economic losses. A previous study analyzing CyHV-3 virulence evolution during serial passages onto carp cell cultures suggested that CyHV-3 evolves, at least in vitro, through an assembly of haplotypes that alternatively become dominant or under-represented. The present study investigates the SV diversity and dynamics in CyHV-3 genome during 99 serial passages in cell culture using, for the first time, ultra-deep whole-genome and amplicon-based sequencing. The results indicate that KHV polymorphism mostly involves SVs. These SVs display a wide distribution along the genome and exhibit high turnover dynamics with a clear bias towards inversion and deletion events. Analysis of the pathogenesis-associated ORF150 region in ten intermediate cell passages highlighted mainly deletion, inversion and insertion variations that deeply altered the structure of ORF150. Our findings indicate that SV turnovers and defective genomes represent key drivers in the viral population dynamics and in vitro evolution of KHV. Thus, the present study can contribute to the basic research needed to design safe live-attenuated vaccines, classically obtained by viral attenuation after serial passages in cell culture.  PY 2022 PD JUN SO Peer Community Journal. Section: Infections SN 2804-3871 PU Centre Mersienne VL 2 DI 10.24072/pcjournal.154 ID 89971 ER EF