diff --git a/papers/2023_bloom_c.md b/papers/2023_bloom_c.md index 52e1ea2..74dc710 100644 --- a/papers/2023_bloom_c.md +++ b/papers/2023_bloom_c.md @@ -9,7 +9,7 @@ journal: "Virus Evolution" doi: "10.1093/ve/veae026" link: "https://academic.oup.com/ve/article/9/2/vead055/7265011" image: "/assets/papers/2023_bloom_c.jpg" -selected: true +selected: false keywords: - "SARS-CoV-2" - "Phylogenetics" diff --git a/papers/2026_ahn.md b/papers/2026_ahn.md index 31b1c38..7572f1c 100644 --- a/papers/2026_ahn.md +++ b/papers/2026_ahn.md @@ -1,16 +1,16 @@ --- layout: paper title: "Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures" -date: "2026-01-05" +date: "2026-03-21" authors: - "Jenny J Ahn" - "Timothy C Yu" - "Bernadeta Dadonaite" - "Caelan E Radford" - "Jesse D Bloom" -journal: "bioRxiv" -doi: "10.64898/2026.01.05.697808" -link: "https://doi.org/10.64898/2026.01.05.697808" +journal: "Virus Evolution" +doi: "10.1093/ve/veag018" +link: "https://doi.org/10.1093/ve/veag018" image: "/assets/papers/2026_ahn.jpg" keywords: - "Influenza" diff --git a/papers/2026_dadonaite.md b/papers/2026_dadonaite.md new file mode 100644 index 0000000..b88ad8d --- /dev/null +++ b/papers/2026_dadonaite.md @@ -0,0 +1,30 @@ +--- +layout: paper +title: "Defining the molecular interaction between influenza hemagglutinin and MHC-II" +date: "2026-07-23" +authors: + - "Bernadeta Dadonaite" + - "Annie Dosey" + - "Jenny J Ahn" + - "Timothy C Yu" + - "Sara A Sunshine" + - "Ariana G Farrell" + - "Neil P King" + - "Jesse D Bloom" +journal: "bioRxiv" +doi: "10.64898/2026.07.17.738765" +link: "https://doi.org/10.64898/2026.07.17.738765" +image: "/assets/papers/2026_dadonaite.png" +keywords: + - "Influenza" + - "Deep mutational scanning" + - "Pseudovirus" +selected: true +--- + +## Abstract + +The hemagglutinin (HA) of some influenza viruses can interact with major histocompatibility complex class II (MHC-II), but how these proteins interact is unclear. Here we demonstrate that diverse H5 HAs can use MHC-II to enter cells, with avian MHC-II enabling more efficient entry than human MHC-II for most H5 HAs. To define the molecular interface, we use pseudovirus deep mutational scanning to measure how mutations to H5 HA affect its interaction with tufted duck MHC-II, and identify mutations that restrict HA to exclusively MHC-II or sialic acid receptors. We leverage identification of H5 HA mutations that increase binding to tufted duck MHC-II to determine a 4.8 Å cryo-EM model of the complex. To support the structural model, we measure how all mutations to tufted duck MHC-II affect its interaction with H5 HA, and find the alpha chain is the dominant determinant but beta chain sites near the peptide-binding groove also contribute. To generalize these findings, we use deep mutational scanning to show that a H7 HA interacts with MHC-II similarly to H5 HA. Finally, we show that H1, H2, H3, and H9 HAs interact with avian or human MHC-II, although interactions vary among strains that evolved in different hosts. + +## Interactive visualizations +The results described in this paper can be interactively visualized at [https://dms-vep.org/Flu-H5N1-American-Wigeon-2021-HA-tufted-duck-MHCII-DMS/](https://dms-vep.org/Flu-H5N1-American-Wigeon-2021-HA-tufted-duck-MHCII-DMS/). diff --git a/posts/2026-07-23_ha_mhcii.md b/posts/2026-07-23_ha_mhcii.md new file mode 100644 index 0000000..16459d6 --- /dev/null +++ b/posts/2026-07-23_ha_mhcii.md @@ -0,0 +1,29 @@ +--- +layout: post +title: Defining the molecular interaction between influenza hemagglutinin and MHC-II +date: 2026-07-23 +author: Jesse Bloom +--- + +We just [posted to bioRxiv](https://doi.org/10.64898/2026.07.17.738765) a new study led by Bernadeta Dadonaite that uses a novel combination of deep mutational scanning and cryo-EM to show how influenza HA interacts with MHC-II. +Many important questions remain about how this interaction evolves and its biological role, and determining its structural basis is a first step towards answering those questions. + +--- + +Influenza hemagglutinin (HA) has long been known to use sialic acid as a receptor, but about 7 years ago it was [shown](https://www.nature.com/articles/s41586-019-0955-3) that some highly diverged bat influenza HAs use MHC-II as their entry receptor. +Subsequently it was shown some H2 and H3 HAs could also use MHC-II. +However, the structural basis of this interaction has remained unclear. + +We first showed that many H5 HAs can bind to avian MHC-II, and then used pseudovirus deep mutational scanning to measure how all mutations to a H5 HA affect entry and binding to tufted duck MHC-II. +This work enabled us to functionally define a surface on the HA head that binds MHC-II. +We then used identification of mutations that increase HA binding to tufted duck MHC-II to solve a cryo-EM structure of the complex. +We also measured how MHC-II mutations affect the interaction. + +Our [preprint](https://doi.org/10.64898/2026.07.17.738765) also has lots of other interesting findings related to HA's ability to interact with MHC-II and how this varies across HAs of many subtypes and MHC-II alleles. + +In addition to reading the preprint, for more details see: + + - [This Bluesky thread](https://bsky.app/profile/jbloomlab.bsky.social/post/3mrdg5udgvk2j), which can be read more easily in [threaded form here](https://skywriter.blue/pages/jbloomlab.bsky.social/post/3mrdg5udgvk2j). + - [This X thread](https://x.com/jbloom_lab/status/2080358310562365796) + +To access and view the data, see the following links: [https://dms-vep.org/Flu-H5N1-American-Wigeon-2021-HA-tufted-duck-MHCII-DMS/](https://dms-vep.org/Flu-H5N1-American-Wigeon-2021-HA-tufted-duck-MHCII-DMS/). diff --git a/public/assets/papers/2026_dadonaite.png b/public/assets/papers/2026_dadonaite.png new file mode 100644 index 0000000..23efc48 Binary files /dev/null and b/public/assets/papers/2026_dadonaite.png differ