Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance

Bernadeta Dadonaite & Jesse Bloom

Fred Hutch Cancer Center / HHMI

These slides: https://slides.com/jbloom/h5-dms-short

HA molecular phenotypes relevant to pandemic risk

Pseudovirus to study all HA mutants

Pseudovirus to study all HA mutants

Library of all HA amino-acid mutations

Deep mutational scanning workflow

We can use data to identify recent mutations that affect HA phenotypes

Example: deep mutational scanning shows mutation A160T (H3 numbering; A172T sequential numbering) reduces neutralization by ferret sera.

As shown on the next slide, that mutation has arisen multiple times in the dairy cattle H5N1 outbreak.

(L122Q, P162Q, T199I)

Neutralization assays with influenza virions validate ferret sera escape observed in deep mutational scanning

For more details...

Interactive results:

https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/

Pre-print: on bioRxiv