Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice

Authors

Matthew J. Pekarek, University of Nebraska-LincolnFollow
Erika M. Petro-Turnquist, University of Nebraska-LincolnFollow
Adam Rubrum, St. Jude Children’s Research HospitalFollow
Richard J. Webby, St. Jude Children’s Research Hospital,Follow
Eric A. Weaver, University of Nebraska-LincolnFollow

ORCID IDs

Matthew J. Pekarek https://orcid.org/0000-0003-3214-4220

Richard J. Webby https://orcid.org/0000-0002-4397-7132

Eric A. Weaver https://orcid.org/0000-0002-5029-0662

Document Type

Article

Date of this Version

2022

Citation

Pekarek, M.J.; Petro-Turnquist, E.M.; Rubrum, A.; Webby, R.J.;Weaver, E.A. Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice. Viruses 2022, 14, 1299. https:// doi.org/10.3390/v14061299

Comments

Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license

Abstract

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research.