#17,995
Influenza viruses are notoriously promiscuous, and when 2 or more subtypes infect the same host, they can reassort; producing a hybrid of the two. Most of the time these reassortments are evolutionary failures, but every once in a while it can produce a more `biologically fit' offspring.
Twice in my lifetime (1957 and 1968) avian flu viruses have reassorted with seasonal flu and launched a human pandemic.
- The first (1957) was H2N2, which According to the CDC `. . . was comprised of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes.'
- In 1968 an avian H3N2 virus emerged (a reassortment of 2 genes from a low path avian influenza H3 virus, and 6 genes from H2N2) which supplanted H2N2 - killed more than a million people during its first year - and continues to spark yearly epidemics more than 50 years later.
Pigs are often cited as the `classic mixing vessel' - and were the source of the 2009 H1N1 pandemic - but increasingly we are seeing flu viruses spreading into new mammalian hosts; including mink, cats, dogs, and marine mammals.
Two months ago, in Virologica Sinica: The Evolution, Pathogenicity & Transmissibility of Quadruple Reassortant H1N2 Swine Influenza Virus in China, we looked at a worrisome report on a Quadruple Reassortant H1N2 virus (2 human, & 2 swine subtypes) circulating in pigs in China, which already replicates efficiently in human, canine, and swine cells and mice.
Today, thanks to a reader who sent me the link, we have another report on the growing diversity of swine flu viruses circulating in pigs, this time in Guangxi, China.
While the Swine-variant EA H1N1 `G4' virus - which we've been following since 2015 - continues to dominate, researchers reported the co-circulation of a number of swine viruses, including the discovery of a novel quadruple reassortant H1N2 virus with an M gene from H9N2.
This discovery is all the more remarkable because it appears that this H9N2 M gene contribution may have come via reverse zoonosis (human-to-animal) transmission of the H7N9 virus (which carries internal genes from H9N2).
While this H1N2 virus doesn't appear to have been `fit' enough to gain a permanent foothold, it illustrates how convoluted, and unpredictable, the evolution of swine viruses has become.
First a link, and some excerpts from the open-access report, after which I'll have a bit more.
Long-term co-circulation of multiple influenza A viruses in pigs, Guangxi, China
Co-circulation of multiple swine influenza viruses in China
Chongqiang Huang,Liangzheng Yu,Yi Xu,Jiamo Huang,Yibin Qin,Xuan Guo,Yongfang Zeng,Yifeng Qin,Kang Ouyang,Zuzhang Wei,Weijian Huang,Adolfo García-Sastre &Ying Chen
Article: 2337673 | Accepted author version posted online: 04 Apr 2024
Cite this article https://doi.org/10.1080/22221751.2024.2337673
Abstract
Influenza A viruses (IAVs) pose a persistent potential threat to human health because of the spillover from avian and swine infections. Extensive surveillance was performed in 12 cities of Guangxi, China, during 2018 and 2023. A total of 2,540 samples (including 2,353 nasal swabs and 187 lung tissues) were collected from 18 pig farms with outbreaks of respiratory disease.
From these, 192 IAV-positive samples and 19 genomic sequences were obtained. We found that the H1 and H3 swine influenza A viruses (swIAVs) of multiple lineages and genotypes have continued to co-cirulate during that time in this region.
Genomic analysis revealed the Eurasian avian-like H1N1 swIAVs (G4) still remained predominant in pig populations. Strikingly, the novel multiple H3N2 genotypes were found to have been generated through repeated introduction of the early H3N2 North American triple reassortant viruses (TR H3N2 lineage) that emerged in USA and Canada in 1998 and 2005, respectively.
Notably, when the matrix gene segment derived from H9N2 avian influenza virus was introduced into endemic swIAVs, this produced a novel quadruple reassortant H1N2 swIAV that could pose a potential risk for zoonotic infection.
(SNIP)
Several lines of evidence showed that EA H1N1 viruses owned the ability of binding to human-type receptors [12] and there were at least 36 human infections with EA H1N1 recorded [11]. In particular, the EA H1N1 swIAVs (genotypes 4 and 5) carrying internal gene segments from pdm09/H1N1 and the triple-reassortant (TR) lineage have become established in the pig population in China [11], and one of these had acquired increased human infectivity [13]. In addition, the pdm/09-like internal gene cassette was successfully incorporated into the swine H3N2 virus, and it had carried the surface genes from the recent human-like H3N2 (HL H3N2) lineage since 2010 [10,14,15].
Importantly, the swine H3 IAVs were found to have been derived from human-like viruses, which had a higher potential to infect humans because they could preferentially bind to the human-type α-2,6 sialic acid receptors [16]. Of note, the pdm/09 internal gene cassette gradually evolved and may act as the TR internal gene (TRIG) cassette to accommodate the suface genes from different origins. More and more novel genotypes with pdm09 internal gene cassette were found in pigs [6,17,18], which increased the risk of pdm09-reassorted viruses with antigenetic diversity to infect humans.
Natural reassortment of a novel swIAV isolate carrying NA gene from TX98-like or ON05-like TR virus and the M gene from avian H9N2 virus
On November 18, 2019, a novel quadruple reassortant [A/Swine/Guangxi/JGS17/2019(H1N2)] was detected in breeding pigs with severe respiratory disease, who showed symptoms of fever, dyspnea and loss of appetite
Analysis of the genotype characterization indicated that their HA gene belonged to pdm09/H1N1 lineage (Figure 4), but it was distinct from the early pdm09/H1N1-like strain (Sw/GX/DX24/13), only sharing 95.2% nt identity. Interestingly, it was found for the first time that the NA gene segment shared high identities with the TX98-like virus circulating in pigs in 1998, which resulted in several outbreaks of severe respiratory disease in USA [25] (Supplementary Figure S1).
Notably, phylogenetic analysis based on the M gene showed that this novel H1N2 swIAV isolate carried a M gene segment from the avian G1-like H9N2 lineage, which was genetically associated with the human H7N9 strain [A/Jiangsu/05155/2016(H7N9)](Figure 3), sharing 98.9% nt identity.
This suggested that the introduction of the avian M gene into pigs could have originated from H7N9-infected humans. Importantly, the reverse zoonotic infection from human to pigs will enrich the endemic swIAVs gene pool and will likely generate novel reassortant viruses which may be continually transmitted between these two species.
(SNIP)
Guangxi province is located in the south of China where there were more than 30 million pigs in 2022 and this region produces approximately 2.2 million tons of pork. International trade and movement of animals bring further unexpected introduction of the earlier existing TR H3N2 swIAVs into the locally circulating swIAVs.
It is worth noting that the TX98-like and ON05-like viruses were introduced into pig populations via imported animals. The NA gene from the human seasonal H3N2 or EA H1N1 viruses was replaced by the early TR H3N2 lineage (ON05-like) and these formed new HL H3N2 viruses, resulting in the generation of four novel genotypes (G11, G19, G24, G25). Importantly, introduction of the H9N2 G1-like M gene into the pdm09/H1N1-like virus (G19) generated a novel quadruple reassortant H1N2 virus.
These findings further emphasize the importance of active surveillance for the local and imported swine herds in order to uncover the emergence of novel swIAV strains which could pose potential threats to human health.
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). For the past 7 years we have seen a rise in H1N2v infections, while prior to 2017 H3N2v was the most commonly reported swine variant virus.
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
EID Journal: Natural Reassortment of EA H1N1 and Avian H9N2 Influenza Viruses in Pigs, China
Surveillance and testing of swine remains rare, even here in the United States and Europe, and while we get occasional research articles, they are often reporting on events or discoveries that occurred years ago (in today's report, the reassortant H1N2 virus was discovered in 2019).
Given the greatly increased diversity of influenza viruses now in circulation, and the growing number of spillovers into mammalian species, the time between influenza pandemics is likely to become shorter in the future (see BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events).Most of the swine-Influenza A viruses (swIAV) that circulate around the world do so largely under our radar. While we watch China, the next swine variant threat could just as easily come from Brazil, or Chile, Europe, or the United States.
Meaning we should be preparing like there's no tomorrow. Because one of these days, there may not be.
