Avian Flu Diary: PNAS: The Genomic Landscape of Swine Influenza A Viruses in Southeast Asia

#17,617

Yesterday, in Influenza A Virus in Pigs in Senegal & Risk Assessment of AIV Emergence and Transmission to Humans, we looked at the unexpectedly high prevalence of antibodies to H5, H7, and H9 avian influenza in pigs tested in Dakar, in 2018-2019.

While we rightfully worry about the potential for an exotic avian virus to adapt to mammals, all of the known influenza pandemics over the past 130 years have come from H1, H2, and H3 viruses.

Viruses that are also highly adapted to, and circulate continuously, in swine. While most swine-origin Influenza viruses don't transmit particularly well in humans, every once in a while a virus hits the genetic jackpot, and is able to expand its host range.

Our 2009 H1N1 pandemic was the result of a triple-reassorted H1N1 virus - which had been circulating quietly in pigs for at least a decade - acquiring the ability to easily infect, and transmit among, humans.

And while surveillance is limited, we know there are a lot of swine flu viruses - most of which remain uncharacterized - circulating in pigs around the globe. In recent months we've looked at swine variant human infections from Taiwan and Brazil, and the United States.

The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).

H1N2 variant [A/California/62/2018] Jul 2019 5.8 5.7 Moderate
H3N2 variant [A/Ohio/13/2017] Jul 2019 6.6 5.8 Moderate
H3N2 variant [A/Indiana/08/2011] Dec 2012 6.0 4.5 Moderate

In 2021 the CDC ranked a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list (see EID Journal: Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020).

But most of the swine-Influenza A viruses (swIAV) that circulate around the world do so under the radar.

Today we've got a new study from a team at Duke-NUS Medical School, Singapore which documents a diverse array of swIAV in Cambodian pigs, with reassorted gene segments from diverse geographical origins (including North America).

It's a long, and at times technical, review - the details of which will be of most interest to virologists. Those wishing a deeper dive should follow the link. I've only reproduced the Abstract and Significance below.

I'll have a brief postscript after the break.

The genomic landscape of swine influenza A viruses in Southeast Asia

Michael A. Zeller , Jordan Ma Foong Ying Wong , +13, and Yvonne C. F. Su yvonne.su@duke-nus.edu.sg

received February 10, 2023; accepted June 7, 2023 August 8, 2023

120 (33) e2301926120
https://doi.org/10.1073/pnas.2301926120

Significance

Influenza A viruses cause significant morbidity and mortality in humans and swine, yet we have limited understanding of how influenza A viruses evolve within pigs in Southeast Asia. Here, we analyzed influenza A virus genomic data collected from pigs in Cambodia, combined with a global dataset, and show the prolonged cryptic circulation of diverse swIAV lineages in Southeast Asia, including some that resulted from reverse zoonotic transmission to pigs that occurred up to 20 B.P. We uncover the breadth of H1 and H3 diversity present in Cambodian swine, identifying the complex genomic reassortment processes and spatial movement of viruses across geographical borders that drive the emergence of new reassortant viruses, posing an undetermined risk to both humans and pigs.

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

(SNIP)

Although we've been understandably focused on avian H5N1 the past few months, swine-origin influenza viruses constitute a plausible pandemic threat, are very much worthy of our attention.

A few recent blogs on these viruses include.

CDC EID Journal: Interspecies Transmission of Swine Influenza A Viruses and Human Seasonal Vaccine-Mediated Protection Investigated in Ferret Model