The genomic landscape of swine influenza A viruses in Southeast Asia

Author:

Zeller Michael A.1ORCID,Ma Jordan1ORCID,Wong Foong Ying1ORCID,Tum Sothyra2,Hidano Arata3ORCID,Holt Hannah3,Chhay Ty4ORCID,Sorn San2,Koeut Dina2ORCID,Seng Bunnary2ORCID,Chao Sovanncheypo2ORCID,Ng Giselle G. K.1ORCID,Yan Zhuang1ORCID,Chou Monidarin5,Rudge James W.3ORCID,Smith Gavin J. D.1678ORCID,Su Yvonne C. F.1ORCID

Affiliation:

1. Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore

2. National Animal Health and Production Research Institute, General Directorate of Animal Health and Production, Phnom Penh 120608, Cambodia

3. Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London WC1E 7HT, United Kingdom

4. Livestock Development for Community Livelihood, Phnom Penh 120108, Cambodia

5. University of Health Sciences, Phnom Penh 120210, Cambodia

6. Centre for Outbreak Preparedness, Duke-NUS Medical School, Singapore 169857, Singapore

7. SingHealth Duke-NUS Global Health Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore 169857, Singapore

8. Duke Global Health Institute, Duke University, Durham, NC 27708

Abstract

Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza A virus (swIAV). Effective surveillance is essential to uncover emerging virus strains; however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia. More than 4,000 nasal swabs were collected from pigs in Cambodia, yielding 72 IAV-positive samples by RT-qPCR and 45 genomic sequences. We unmasked the cocirculation of multiple lineages of genetically diverse swIAV of pandemic concern. Genomic analyses revealed a novel European avian-like H1N2 swIAV reassortant variant with North American triple reassortant internal genes, that emerged approximately seven years before its first detection in pigs in 2021. Using phylogeographic reconstruction, we identified south central China as the dominant source of swine viruses disseminated to other regions in China and Southeast Asia. We also identified nine distinct swIAV lineages in Cambodia, which diverged from their closest ancestors between two and 15 B.P., indicating significant undetected diversity in the region, including reverse zoonoses of human H1N1/2009 pandemic and H3N2 viruses. A similar period of cryptic circulation of swIAVs occurred in the decades before the H1N1/2009 pandemic. The hidden diversity of swIAV observed here further emphasizes the complex underlying evolutionary processes present in this region, reinforcing the importance of genomic surveillance at the human–swine interface for early warning of disease emergence to avoid future pandemics.

Funder

DOD | Defense Threat Reduction Agency

HHS | NIH | National Institute of Allergy and Infectious Diseases

Ministry of Health -Singapore

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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