Abstract
Influenza B virus primarily infects humans, causing seasonal epidemics globally. Two antigenic variants-Victoria-like and Yamagata-like-were detected in the 1980s, of which the molecular basis of emergence is still incompletely understood. Here, the antigenic properties of a unique collection of historical virus isolates, sampled from 1962 to 2000 and passaged exclusively in mammalian cells to preserve antigenic properties, were determined with the hemagglutination inhibition assay and an antigenic map was built to quantify and visualize the divergence of the lineages. The antigenic map revealed only three distinct antigenic clusters-Early, Victoria, and Yamagata-with relatively little antigenic diversity in each cluster until 2000. Viruses with Victoria-like antigenic properties emerged around 1972 and diversified subsequently into two genetic lineages. Viruses with Yamagata-like antigenic properties evolved from one lineage and became clearly antigenically distinct from the Victoria-like viruses around 1988. Recombinant mutant viruses were tested to show that insertions and deletions (indels), as observed frequently in influenza B virus hemagglutinin, had little effect on antigenic properties. In contrast, amino-acid substitutions at positions 148, 149, 150, and 203, adjacent to the hemagglutinin receptor binding site, determined the main antigenic differences between the Early, Victoria-like, and Yamagata-like viruses. Surprisingly, substitutions at two of the four positions reverted in recent viruses of the Victoria lineage, resulting in antigenic properties similar to viruses circulating ∼50 y earlier. These data shed light on the antigenic diversification of influenza viruses and suggest there may be limits to the antigenic evolution of influenza B virus.
| Original language | English |
|---|---|
| Article number | e2211616119 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 119 |
| Issue number | 42 |
| DOIs | |
| Publication status | Published - 10 Oct 2022 |
Bibliographical note
Funding Information:ACKNOWLEDGMENTS. We thank Prof. Yoshihiro Kawaoka for sharing the high-yield influenza B reverse genetics system and hemagglutinin and neuraminidase gene-encoding plasmids used in this study and Dr. Sam Wilks for support with the Racmacs R package for antigenic cartography. We gratefully acknowledge the authors from the originating laboratories responsible for obtaining the specimens and the submitting laboratories where genetic sequence date were generated and shared via the GISAID Initiative, on which this research is based. This work was supported by the National Institute of Allergy and Infectious Diseases–NIH Centers of Excellence for Influenza Research and Response contract 75N93021C00014 and HHSN272201400008C and by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 874735 (Versatile Emerging Infectious Disease Observatory). The funders had no role in the study design, data collection and interpretation, or decision to submit the data for publication.
Publisher Copyright:
Copyright © 2022 the Author(s). Published by PNAS.