Tuesday, July 12, 2022

EID Journal: Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020



If it seems as if we are suddenly hearing a lot more about the zoonotic potential of swine influenza viruses circulating in China the past year or so, you'd be right. 

The threat isn't new, of course, but as swine flu viruses reassort and diversify, their threat naturally increases.

In late 2015 Chinese and Japanese researchers made headlines when they isolated and characterized a number of avian H1N1 virus variants circulating in Chinese pigs that they believed had considerable pandemic potential (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza) 

Two years ago, researchers writing in PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China, 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's Responds to the PNAS EA H1N1 `G4' Swine Flu Study

ECDC Risk Assessment: Eurasian avian-like A(H1N1) swine influenza viruses

WHO Novel Flu Summary & Risk Assessment - July 2020

FAO/OIE/WHO Tripartite Statement on the Pandemic Risk of Swine Influenza

In early 2021, the CDC Selected Swine-Variant EA H1N1 Virus For The Top Of Their IRAT List of novel flu viruses with pandemic potential. 

Twice last month we looked at concerning research on EAH1N1 swine-influenza viruses in China. 

EID Journal: Natural Reassortment of EA H1N1 and Avian H9N2 Influenza Viruses in Pigs, China

EID Journal: Potential Threats to Human Health from EA H1N1 Viruses and Reassortants

To all of this we can add this latest Dispatch published in the CDC's EID Journal, reporting on 2 EA H1N1 `G4' type viruses in Chinese pigs, including one that shows substantial zoonotic potential. 

I've only posted some excerpts from the report, so you'll want to follow the link to read it in its entirety.  I'll have a brief postscript after the break. 

Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020

Min Gu1, Kaibiao Chen1, Zhichuang Ge, Jun Jiao, Tianyu Cai, Suhan Liu, Xiaoquan Wang, Xinan Jiao, Daxin Peng, and Xiufan Liu 


We investigated genetic and biologic characteristics of 2 Eurasian avian-like H1N1 swine influenza viruses from pigs in China that belong to the predominant G4 genotype. One swine isolate exhibited strikingly great homology to contemporaneous human Eurasian avian-like H1N1 isolates, preferential binding to the human-type receptor, and vigorous replication in mice without adaptation.

Pigs have long been considered a crucial genetic mixing vessel for influenza A viruses (IAVs) of different hosts (1) because of the dual expression of human (SAα-2,6Gal) and avian (SAα-2,3Gal) viral receptors on their respiratory epithelium. Swine IAVs such as H1N1 and H3N2 subtypes sporadically infect humans and are prone to cause bidirectional interspecies transmission at the swine–human interface (25).
So far, Eurasian avian-like (EA) H1N1 has dominated prevalence in pig herds in China and caused >10 human infections (69). In particular, the dominant genotype 4 (G4) EA H1N1 containing 2009 pandemic influenza A(H1N1) polymerase basic (PB) 1 and 2, polymerase acid (PA), nucleoprotein (NP), and matrix (M) genes, plus the triple-reassortant (TR) nonstructural (NS) gene, is thought to be a candidate virus of potential pandemic (10,11). Indeed, a case of human infection with G4 EA H1N1 was reported in Yunan Province, China, in 2021 (8). It is imperative to conduct surveillance on swine IAVs and evaluate their risk to public health.

The Study

During monthly surveillance of swine IAVs in China during October–December 2020, we collected a total of 376 nasal swab samples from apparently healthy pigs in a slaughterhouse accommodating swine from neighboring regions (Jiangsu, Shandong, and Anhui Provinces in eastern China).
We detected H1 subtype swine influenza virus in 9 of those by real-time reverse transcription quantitative PCR; 2 were confirmed as hemagglutinin (HA) positive after inoculating into MDCK cells (12). We further evaluated these 2 swine IAV isolates, A/swine/Jiangsu/HD11/2020 (H1N1) [HD11] and A/swine/Anhui/HD21/2020 (H1N1) [HD21], for their genetic and biologic characteristics.



Homology alignment and phylogenetic tree construction analysis suggest that HD11 and HD21, two G4 EA H1N1 swine IAVs isolated in 2020 in China, are strongly related to recent human-origin EA H1N1 viruses. In particular,
HD11 had higher affinity for human-type 6ʹSLN at the level that is equivalent to the human seasonal H3N2 virus. Moreover, HD11 replicated much faster in vitro in MDCK cells and in vivo in the lung than di HD21 and was highly pathogenic to BALB/c mice, as evidenced by its lethality, higher viral loads in pulmonary tissues, and higher levels of inflammatory cytokines in the lung.
We propose that the HD11-like G4 swine isolates whose genomic sequences share great homology with that of contemporaneous human EA H1N1 viruses may lead to interspecies transmission. Therefore, the public health threat from the zoonotic G4 EA H1N1 viruses should not be underestimated.


While we often get excellent scientific papers out of China, real-time reporting of outbreaks of avian or swine influenza is far less robust.  China's last announced avian influenza outbreak (H5N1) in waterfowl was in November of 2021, and you have to go back well over a year to find mention of an outbreak in poultry on their MOA Emergencies website.

Novel flu infections in humans are only sporadically reported, and often weeks or even months after the fact (see The Lancet: Resurgence of H5N6 Avian Influenza Virus in 2021 Poses New Threat to Public Health).

While it is certainly possible that we could be blindsided by another coronavirus - or something even more exotic, like Nipah, or an H5 or H7 avian virus - if you want to play the odds, the next pandemic will more than likely come from a reassortant H1, H2, or H3 virus.

And while China doesn't have a monopoly on swine viruses, China's EA H1N1 appears to be the current favorite in the pandemic flu sweepstakes.