# Evaluation of pandemic potential of the genotype 4 (G4) swine influenza virus using ex vivo and in vitro cultures of the human respiratory tract

**Authors:** Jenny C.M. Chan, Rachel H.H. Ching, Hermione H.M. Kock, Teng Long, John M. Nicholls, J.S. Malik Peiris, Kenrie P.Y. Hui, Michael C.W. Chan

PMC · DOI: 10.1099/jgv.0.002133 · The Journal of General Virology · 2025-07-31

## TL;DR

This study evaluates the pandemic potential of a swine influenza virus (G4) by testing its replication and immune response in human respiratory tissues and macrophages.

## Contribution

The study provides empirical evidence on the replication competence and cytokine induction of G4 swine influenza in human respiratory models.

## Key findings

- G4 strains replicate in human lung and bronchus ex vivo with similar efficiency to the 2009 pandemic H1N1 strain.
- G4 strains induce cytokine responses in macrophages comparable to the 2009 pandemic H1N1 strain.
- The findings suggest that G4 swine influenza may pose a notable public health threat to humans.

## Abstract

Recent studies have reported a genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus in swine, demonstrating a potential pandemic threat in humans. Here, we have compared the tropism, replication competence and pro-inflammatory cytokine and chemokine induction of the two G4 EA H1N1 strains in parallel with 2009 pandemic H1N1 (H1N1/pdm/09) and A/Quail/HK/G1/1997 H9N2 (G1) using ex vivo culture of the human respiratory tract and in vitro culture of human peripheral blood-derived macrophages. Our results showed that G4 strains could replicate in ex vivo cultures of human lung and bronchus with a similar replication competence to H1N1/pdm/09. The cytokine induction levels of G4 were similar to H1N1/pdm/09 in macrophages. Taken together, we could extrapolate that the G4 EA H1N1 swine influenza may pose a notable public health threat towards human and should not underestimate this threat.

## Linked entities

- **Diseases:** influenza (MONDO:0005812)
- **Species:** Homo sapiens (taxon 9606), Sus scrofa (taxon 9823)

## Full-text entities

- **Diseases:** inflammatory (MESH:D007249)
- **Species:** Sus scrofa (pig, species) [taxon 9823], Swine influenza virus (species) [taxon 12845], Homo sapiens (human, species) [taxon 9606], H1N1 subtype (serotype) [taxon 114727], H9N2 subtype (serotype) [taxon 102796]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12313140/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12313140/full.md

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Source: https://tomesphere.com/paper/PMC12313140