# Impact of an amino acid deletion detected in the hemagglutinin (HA) antigenic site of swine influenza A virus field strains on HA antigenicity

**Authors:** Taichi Nakano, Mana Esaki, Akiha Inoue, Fumiko Koike, Kosuke Okuya, Makoto Ozawa

PMC · DOI: 10.1128/jvi.01820-25 · 2026-02-19

## TL;DR

A deletion in a key protein of swine influenza A virus changes how the immune system recognizes it, without affecting virus growth.

## Contribution

The study reveals that a naturally occurring amino acid deletion in the HA protein of swine influenza A virus significantly alters antigenicity.

## Key findings

- Amino acid deletion at position 155 in H1 HA does not significantly impact viral replication in vitro.
- The deletion at position 155 markedly alters HA antigenicity, as shown by neutralization titers.
- Such antigenic changes may allow the virus to evade existing immunity and increase zoonotic risk.

## Abstract

Swine influenza A virus (swIAV) is an important pathogen with regard to both the swine industry and public health. The pandemic A(H1N1) 2009 outbreak was caused by the swine-origin pandemic A(H1N1) 2009 [A(H1N1)pdm09] virus. Several reports have shown that several amino acid substitutions in the hemagglutinin (HA) antigenic sites can alter HA antigenicity. However, the impact of the amino acid deletion at position 155 on HA antigenicity remains unknown. In this study, we have isolated 11 samples of swIAVs from seven pig farms in Japan and found an amino acid deletion at position 155 of the HA region in one of the isolates of the H1N2 subtype. To examine the impact of this amino acid deletion on viral replication and HA antigenicity, we generated recombinant influenza A viruses possessing the H1 HA gene encoding either an artificial insertion or deletion of glycine at position 155. The growth kinetics of these recombinant viruses in two different cell lines demonstrated that the effect of amino acid deletion at position 155 of H1 HA on viral replication is limited. In contrast, microneutralization assay-based neutralization titers revealed that amino acid deletion significantly altered HA antigenicity. These results demonstrate that a naturally occurring amino acid deletion at position 155 in an H1 HA antigenic site can markedly alter HA antigenicity with only a limited impact on replication in vitro, highlighting the need to monitor such variants in swine populations and to assess their zoonotic potential.

Influenza A viruses circulating in pigs are of major concern because they can reduce herd productivity and sometimes infect humans. Understanding how these viruses change their surface proteins is essential for predicting their evolution and preventing outbreaks. This study focuses on swine influenza A virus isolated from pig farms in Japan and investigates the effect of a specific amino acid deletion in the hemagglutinin protein, which plays a key role in viral recognition by the host immune system. The results show that this deletion does not greatly affect virus growth but markedly alters how the immune system recognizes the virus. Such antigenic changes may allow the virus to evade existing immunity in pig populations and potentially increase the risk of transmission to humans. These findings underscore the need for continued surveillance of such variants in pigs and for future studies to evaluate their possible zoonotic implications.

## Linked entities

- **Proteins:** ha (hair bristles)

## Full-text entities

- **Species:** Sus scrofa (pig, species) [taxon 9823], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** deletion at position 155, deletion of glycine at position 155

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13011390/full.md

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Source: https://tomesphere.com/paper/PMC13011390