While H5Nx remains atop most people's pandemic worry list, it is far from the only viral contender making concerning moves in the wild. Even among the narrow field of influenza A viruses, H5N1 ranks fairly far down the CDC's IRAT list.
In terms of likelihood of emergence, the CDC currently ranks a Chinese EA H1N1 `G4' swine virus at the very top of their list of zoonotic influenza A viruses with pandemic potential, with 3 other North American swine variant viruses scoring higher than H5N1.
Trying to second guess which virus will reach the finish line next is a bit of a mug's game; particularly given our current level of surveillance and data sharing. Suffice to say: eventually, another pandemic will emerge.
In the `Significance' section the authors boiled it down to this:The world's attention was first drawn to this emerging swine-origin virus in late 2015, when a group of Chinese scientists (including Hualan Chen) published a paper in PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza describing its prevalence, genetics, and transmissibility (in ferrets).
Here, we found that, after long-term evolution in pigs, the EAH1N1 SIVs have obtained the traits to cause a human influenza pandemic.
Since then we've followed numerous studies on this emerging virus, including a 2020 study in PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China, which reported > 10% seroprevalence for the EAH1N1 among swine workers tested, suggesting that EAH1N1 was gaining in its ability to jump species.
This report led to a flurry of `risk assessments' by public health agencies on EA H1N1 `G4', including the CDC, the ECDC and an FAO/OIE/WHO Tripartite Statement.
In early 2021 the CDC ranked a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list, and since then we've seen additional studies that have only exacerbated concerns.
Our last in-depth look at this EA H1Nx G4 strain was just five weeks ago, in J. Gen. Virology: Evaluation of Pandemic Potential of the Genotype 4 (G4) Swine Influenza Virus using Ex Vivo and In Vitro Cultures of the Human Respiratory Tract.
This is a lengthy, detailed, and at times technical report, and I've only posted the abstract and some excerpt Those wishing a deeper dive will want to follow the link to read it in its entirety.
I'll have a brief postscript after the break.
Continuous evolution of Eurasian avian-like H1N1 swine influenza viruses with pdm/09-derived internal genes enhances pathogenicity in mice
Authors: Riguo Lan , Jizhe Yang, Jixiang Li, Han Li, Xihao Cao, Mengyan Tao, Haoyu Chang, Haili Yu, Qi Tong, Lu Lu, Jinhua Liu , Honglei Sun shlei668@163.comAuthors Info & Affiliations
https://doi.org/10.1128/jvi.00430-25
PDF/EPUB
ABSTRACT
Swine influenza A virus (swIAV) is an important zoonotic pathogen with the potential to cause human influenza pandemics. Swine are considered “mixing vessels” for generating novel reassortant influenza A viruses. In 2009, a swine-origin reassortant virus (2009 pandemic H1N1, pdm/09 H1N1) spilled over to humans, causing a global influenza pandemic. This virus soon spread back into swine herds and reassorted with the circulating swIAVs. We previously reported that the genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bore pdm/09- and triple reassortant (TR)-derived internal genes, had been predominant in swine populations of China since 2016, posing a threat to both the swine industry and public health.Here, our ongoing surveillance confirmed that G4 EA H1N1 viruses remained the predominant swIAVs in China from 2019 to 2023 and had reassorted with the co-circulating swIAVs, such as the H3N2 virus, to generate novel reassortant EA H1N2 viruses.
Genetic analyses revealed that the pdm/09-derived internal genes of G4 EA H1N1 viruses originated from reassortments between pdm/09 H1N1 and EA H1N1 viruses in 2009–2010 and underwent independent and continuous evolution in the swine host, exhibiting higher evolutionary rates than those of the pdm/09 H1N1 virus circulating in humans.
The accelerated evolution of internal genes enhanced the polymerase activity of G4 EA H1N1 viruses in mammalian cells, resulting in increased viral replication and pathogenicity in mice. This study provides evidence for swine in promoting the genetic evolution of influenza A virus and highlights the need for increased attention to novel reassortant viruses in swine.
IMPORTANCE
The emergence of pdm/09 H1N1 virus highlights the role of swine influenza A viruses (swIAVs) in generating novel influenza viruses with pandemic potential. Since 2009, the pdm/09 H1N1 virus has been frequently transmitted to swine and reassorted with the circulating swIAVs, generating many new reassortant viruses bearing pdm/09-derived genes globally. The G4 EA H1N1 viruses, which bore pdm/09-derived internal genes and acquired increased human infectivity, remained the predominant swIAVs in China from 2019 to 2023 and reassorted with the co-circulating swIAVs to generate novel subtype viruses. The internal genes of G4 EA H1N1 viruses originated from the human pdm/09 H1N1 viruses during 2009–2010 and exhibited higher evolutionary rates and greater genetic diversity than those in the human host. This has contributed to increased viral adaptation and pathogenicity in mammals. Therefore, sustained surveillance and immunization efforts are essential to control emerging reassortant swIAVs and protect public health.
In summary, our findings show that the independent and accelerated evolution of pdm/09-derived internal genes within the swine host has enhanced both the infectivity and pathogenicity of the G4 EA H1N1 virus to mice. These G4 EA H1N1 viruses contribute to the emergence of novel reassortant viruses, thereby increasing the risk to human public health. Consequently, implementing continuous surveillance and proactive immunization strategies is essential to control these viruses. These steps are crucial for managing novel reassortant swIAVs and preventing future human pandemics.
In last month's report we learned that EA H1N1 G4 replicates competently in human bronchial and lung tissue explants, which would allow for both upper and lower respiratory infections.
It also binds preferentially to a2,6-linked sialic acid receptors cells, which are abundant in the human upper airway. Past studies suggest that population immunity to these EA H1Nx viruses would be low.
While there are reasons to believe EA H1N1 might not produce as severe of a pandemic (in terms of mortality) as an avian H5 or H7 pandemic virus, even a 1%-2% CFR - when combined with a high attack rate - would present a grave threat.
But as far as I can see, the world isn't even remotely ready for that level of a pandemic, much less something on the level of SARS-CoV, MERS-CoV, or H5Nx.
Which is why I continue to promote personal preparedness (see A Personal Pre-Pandemic Plan).
