add 2025_yu paper on H3 DMS and epistasis

papers/2025_yu.md

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+---
+layout: paper
+title: "Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin"
+date: "2025-05-24"
+authors: 
+    - "Timothy C Yu"
+    - "Caroline Kikawa"
+    - "Bernadeta Dadonaite"
+    - "Andrea N Loes"
+    - "Janet A Englund"
+    - "Jesse D Bloom"
+journal: "bioRxiv"
+doi: "10.1101/2025.05.24.655919"
+link: "https://doi.org/10.1101/2025.05.24.655919"
+image: "/assets/papers/2025_yu.jpg"
+keywords:
+    - "Influenza"
+    - "Epistasis"
+    - "Deep mutational scanning"
+    - "Pseudovirus"
+selected: false
+---
+
+## Abstract
+The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability. Epistasis shapes this evolution, as an antigenic mutation that is deleterious in one genetic background may become tolerated in another. However, the extent to which epistasis can alleviate pleiotropic conflicts between immune escape and protein function/stability is unclear. Here, we measure how all amino acid mutations in the HA of a recent human H3N2 influenza strain affect its cell entry function, acid stability, and neutralization by human serum antibodies. We find that epistasis has enabled emergence of antigenic mutations that were detrimental to HA’s cell entry function in earlier strains. However, epistasis appears insufficient to overcome the pleiotropic costs of antigenic mutations that impair HA’s stability, explaining why some mutations that strongly escape human antibodies never fix in nature. Our results refine our understanding of the mutational constraints that shape influenza evolution: epistasis can enable antigenic change, but pleiotropic effects can restrict its trajectory.

posts/2025-05-27_yu-h3.md

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+---
+layout: post
+title: Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin
+date: 2025-05-27
+author: Jesse Bloom
+---
+
+In a new study led by grad student Tim Yu and [posted on bioRxiv today](https://www.biorxiv.org/content/10.1101/2025.05.24.655919v1), we used pseudovirus deep mutational scanning to measure how all mutations to a recent H3N2 HA affect cell entry, stability, and antibody escape.
+The results help shed light on how the pleiotropic effects of mutations shape influenza evolution.
+
+---
+
+For accessible summaries of the study, see:
+
+  - [This Bluesky thread](https://bsky.app/profile/jbloomlab.bsky.social/post/3lq63xmb5kc2r), which can be read more easily in [threaded form here](https://skywriter.blue/pages/jbloomlab.bsky.social/post/3lq63xmb5kc2r).
+  - [This X thread](https://x.com/jbloom_lab/status/1927399924519367090)
+
+All the data are available for interactive visualization and download at [https://dms-vep.org/Flu_H3_Massachusetts2022_DMS/](https://dms-vep.org/Flu_H3_Massachusetts2022_DMS/)