tetano
Editor, Senior Moderator
Cell Host Microbe
. 2024 Jul 16:S1931-3128(24)00233-6.
doi: 10.1016/j.chom.2024.06.015. Online ahead of print. Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin
Frances C Welsh[SUP] 1 [/SUP], Rachel T Eguia[SUP] 2 [/SUP], Juhye M Lee[SUP] 2 [/SUP], Hugh K Haddox[SUP] 3 [/SUP], Jared Galloway[SUP] 3 [/SUP], Nguyen Van Vinh Chau[SUP] 4 [/SUP], Andrea N Loes[SUP] 2 [/SUP], John Huddleston[SUP] 5 [/SUP], Timothy C Yu[SUP] 1 [/SUP], Mai Quynh Le[SUP] 6 [/SUP], Nguyen T D Nhat[SUP] 7 [/SUP], Nguyen Thi Le Thanh[SUP] 4 [/SUP], Alexander L Greninger[SUP] 8 [/SUP], Helen Y Chu[SUP] 9 [/SUP], Janet A Englund[SUP] 10 [/SUP], Trevor Bedford[SUP] 11 [/SUP], Frederick A Matsen 4th[SUP] 2 [/SUP], Maciej F Boni[SUP] 12 [/SUP], Jesse D Bloom[SUP] 13 [/SUP]
Affiliations
Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.
Keywords: antigenic evolution; deep mutational scanning; hemagglutinin; immune selection; influenza; serum antibodies.
. 2024 Jul 16:S1931-3128(24)00233-6.
doi: 10.1016/j.chom.2024.06.015. Online ahead of print. Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin
Frances C Welsh[SUP] 1 [/SUP], Rachel T Eguia[SUP] 2 [/SUP], Juhye M Lee[SUP] 2 [/SUP], Hugh K Haddox[SUP] 3 [/SUP], Jared Galloway[SUP] 3 [/SUP], Nguyen Van Vinh Chau[SUP] 4 [/SUP], Andrea N Loes[SUP] 2 [/SUP], John Huddleston[SUP] 5 [/SUP], Timothy C Yu[SUP] 1 [/SUP], Mai Quynh Le[SUP] 6 [/SUP], Nguyen T D Nhat[SUP] 7 [/SUP], Nguyen Thi Le Thanh[SUP] 4 [/SUP], Alexander L Greninger[SUP] 8 [/SUP], Helen Y Chu[SUP] 9 [/SUP], Janet A Englund[SUP] 10 [/SUP], Trevor Bedford[SUP] 11 [/SUP], Frederick A Matsen 4th[SUP] 2 [/SUP], Maciej F Boni[SUP] 12 [/SUP], Jesse D Bloom[SUP] 13 [/SUP]
Affiliations
- PMID: 39032493
- DOI: 10.1016/j.chom.2024.06.015
Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.
Keywords: antigenic evolution; deep mutational scanning; hemagglutinin; immune selection; influenza; serum antibodies.