Virus-induced interference as a means for accelerating fitness-based selection of cyprinid herpesvirus 3 single nucleotide variants in vitro and in vivo

Gao, Y. et al. (2023) Virus-induced interference as a means for accelerating fitness-based selection of cyprinid herpesvirus 3 single nucleotide variants in vitro and in vivo. Virus Evolution, 9(1), vead003. (doi: 10.1093/ve/vead003) (PMID:36816049) (PMCID:PMC9936792)

Abstract

Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses and is advantageous to research because, unlike many herpesviruses, it can be studied in the laboratory by infection of the natural host (common and koi carp). Previous studies have reported a negative correlation among CyHV-3 strains between viral growth in vitro (in cell culture) and virulence in vivo (in fish). This suggests the existence of genovariants conferring enhanced fitness in vitro but reduced fitness in vivo, and vice versa. Here, we identified syncytial plaque formation in vitro as a common trait of CyHV-3 strains adapted to cell culture. Comparison of the sequences of virion transmembrane protein genes in CyHV-3 strains, and the use of various recombinant viruses, demonstrated that this trait is linked to a single nucleotide polymorphism (SNP) in the ORF131 coding sequence (C225791T mutation) that results in codon 183 encoding either an alanine (183A) or a threonine (183T) residue. In experiments involving infections with recombinant viruses differing only by this SNP, the 183A genovariant associated with syncytial plaque formation was the more fit in vitro but the less fit in vivo. In experiments involving co-infection with both viruses, it was observed that in addition to the more fit genovariant contributing to the purifying selection of the less fit genovariant by outcompeting the latter, we observed that this process may be accelerated by viral stimulation of interference at a cellular level, and stimulation of resistance to superinfection at a host level. Collectively, this study illustrates how the fundamental biological properties of some viruses and their hosts may have a profound impact on the degree of diversity that arises within viral populations.

• Item Type: Articles
• Keywords: Herpesvirus, alloherpesvirus, virus evolution, fitness-based selection, purifying selection.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Suarez, Dr Nicolas and Davison, Professor Andrew
• Authors: Gao, Y., Sridhar, A., Bernard, N., He, B., Zhang, H., Pirotte, S., Desmecht, S., Vancsok, C., Boutier, M., Suárez, N. M., Davison, A. J., Donohoe, O., and Vanderplasschen, A. F.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Virus Evolution
• Publisher: Oxford University Press
• ISSN: 2057-1577
• ISSN (Online): 2057-1577
• Published Online: 17 January 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Virus Evolution 9(1): vead003
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172630003		Persistent Infections (Programme 2)	Andrew Davison	Medical Research Council (MRC)	MC_UU_12014/3	III - Centre for Virus Research