Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin,Cell Host & Microbe

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Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-07-19 , DOI: 10.1016/j.chom.2024.06.015
Frances C Welsh ₁ , Rachel T Eguia ₂ , Juhye M Lee ₂ , Hugh K Haddox ₃ , Jared Galloway ₃ , Nguyen Van Vinh Chau ₄ , Andrea N Loes ₂ , John Huddleston ₅ , Timothy C Yu ₁ , Mai Quynh Le ₆ , Nguyen T D Nhat ₇ , Nguyen Thi Le Thanh ₄ , Alexander L Greninger ₈ , Helen Y Chu ₉ , Janet A Englund ₁₀ , Trevor Bedford ₁₁ , Frederick A Matsen ₂ , Maciej F Boni ₁₂ , Jesse D Bloom ₂

Affiliation

Molecular and Cellular Biology Graduate Program, University of Washington, and Basic Sciences Division, Fred Hutch Cancer Center, Seattle, WA 98109, USA; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA.
Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
National Institutes for Hygiene and Epidemiology, Hanoi, Vietnam.
Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA; Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA 98195, USA.
Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA 98195, USA.
Seattle Children's Research Institute, Seattle, WA 98109, USA.
Howard Hughes Medical Institute, Seattle, WA 98109, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.

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.

更新日期：2024-07-19

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