|
|
Hokkaido University Collection of Scholarly and Academic Papers >
International Institute for Zoonosis Control >
Peer-reviewed Journal Articles, etc >
Gene Segment Interactions Can Drive the Emergence of Dominant Yet Suboptimal Gene Constellations During Influenza Virus Reassortment
| Title: | Gene Segment Interactions Can Drive the Emergence of Dominant Yet Suboptimal Gene Constellations During Influenza Virus Reassortment |
| Authors: | Trifkovic, Sanja Browse this author | | Gilbertson, Brad Browse this author | | Fairmaid, Emily Browse this author | | Cobbin, Joanna Browse this author | | Rockman, Steven Browse this author | | Brown, Lorena E. E. Browse this author |
| Keywords: | influenza virus | | reassortment | | pandemics | | gene segment interactions | | vaccine production |
| Issue Date: | 14-Jul-2021 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in microbiology |
| Volume: | 12 |
| Start Page: | 683152 |
| Publisher DOI: | 10.3389/fmicb.2021.683152 |
| Abstract: | A segmented genome enables influenza virus to undergo reassortment when two viruses infect the same cell. Although reassortment is involved in the creation of pandemic influenza strains and is routinely used to produce influenza vaccines, our understanding of the factors that drive the emergence of dominant gene constellations during this process is incomplete. Recently, we defined a spectrum of interactions between the gene segments of the A/Udorn/307/72 (H3N2) (Udorn) strain that occur within virus particles, a major interaction being between the NA and PB1 gene segments. In addition, we showed that the Udorn PB1 is preferentially incorporated into reassortant viruses that express the Udorn NA. Here we use an influenza vaccine seed production model where eggs are coinfected with Udorn and the high yielding A/Puerto Rico/8/34 (H1N1) (PR8) virus and track viral genotypes through the reassortment process under antibody selective pressure to determine the impact of Udorn NA-PB1 co-selection. We discovered that 86% of the reassortants contained the PB1 from the Udorn parent after the initial co-infection and this bias towards Udorn PB1 was maintained after two further passages. Included in these were certain gene constellations containing Udorn HA, NA, and PB1 that confered low replicative fitness yet rapidly became dominant at the expense of more fit progeny, even when co-infection ratios of the two viruses favoured PR8. Fitness was not compromised, however, in the corresponding reassortants that also contained Udorn NP. Of particular note is the observation that relatively unfit reassortants could still fulfil the role of vaccine seed candidates as they provided high haemagglutinin (HA) antigen yields through co-production of non-infectious particles and/or by more HA molecules per virion. Our data illustrate the dynamics and complexity of reassortment and highlight how major gene segment interactions formed during packaging, in addition to antibody pressure, initially restrict the reassortant viruses that are formed. |
| Rights: | Copyright © 2021 Trifkovic, Gilbertson, Fairmaid, Cobbin, Rockman and Brown. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82646 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
|
