A new pandemic? Swine influenza virus seen in China could go global, experts call for urgent steps to control it
While swine influenza viruses usually sicken only pigs, potentially one might also spark a pandemic in people as occurred with the 2009 H1N1 influenza virus. Researchers have now identified a swine influenza virus prevalent in China, which they warn has the potential for pandemic spread in humans. They say measures to control this virus in pigs and closely monitor human populations, especially pig farm workers, must be swiftly implemented.
Why this study?
Pandemic influenza occurs when viruses jump from animal reservoirs to humans. With no prior exposure to the virus, most people do not have immunity to these viruses. Pigs are considered as a key intermediate host or “mixing vessel,” in the development of pandemic influenza viruses. Since not many long-term studies have surveyed flu viruses in swine, gaps exist in what is known about the evolution of swine influenza viruses (SIVs) and the conditions that enable a swine virus to infect humans and cause disease. Previous studies have identified different lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1 and pandemic H1N1. Research has also shown that three major swine influenza virus lineages -- classical, Eurasian avian-like and triple reassortant -- have crossed geographic boundaries, including continents. Accordingly, systemic surveillance of swine influenza viruses can help anticipate and prepare for human pandemics, say experts.
“Influenza A Virus (IAV) is a global pathogen of humans and a wide range of mammalian and avian species. Historically, pandemic IAVs from 1957, 1968 and 2009 are all reassortants derived from human and animal influenza viruses. China has, arguably, the most complex swine influenza viruses ecosystem with classical swine lineage, North American triple-reassortant (TR) lineage, and Eurasian avian-like (EA) lineage SIVs cocirculating in pigs,” write authors in the study published in the Proceedings of the National Academy of Sciences (PNAS).
The team includes experts from Chinese institutes such as China Agricultural University, Shandong Agricultural University, Chinese Center for Disease Control and Prevention, World Health Organization Collaborating Center for Reference and Research on Influenza, and Chinese Academy of Sciences, as well as the University of Nottingham, UK. “Pigs, being susceptible to avian, swine and human IAVs, are regarded as “mixing vessels” in the generation of influenza viruses with pandemic potential. The emergence of the 2009 pandemic (pdm/09) H1N1 virus vividly illustrates the importance of pigs in new outbreaks. Therefore, continuous surveillance of swine influenza viruses in pigs and assessment of their zoonotic potential is essential for early warning and preparedness of human pandemics,” they emphasize.
In the current study, the research team conducted an extensive swine influenza virus surveillance program and isolated 179 swine influenza viruses from pigs across 10 provinces in China from 2011 to 2018. This includes Anhui, Beijing, Hebei, Heilongjiang, Henan, Jiangsu, Jilin, Liaoning, Shandong and Tianjin.
What did the researchers find?
The authors grouped the viruses into six genotypes, with the genotype resembling the Eurasian-avian H1N1 (EA H1N1) lineage (G1) predominating from 2011 to 2013. However, since 2016 the predominant viral genotype has been one incorporating elements from both the 2009 pandemic lineage and the North American triple-reassortant lineage. According to the authors, viruses of this genotype, labeled G4 EA H1N1 by them, exhibited features characteristic of the 2009 pandemic lineage. This includes preferential binding to a human-like receptor and efficient replication in human airway epithelial cells. Airway epithelial cells are the most abundant cell type in the lung and the first to encounter inhaled substances and are, therefore, important in the regulation of host defense. Inhaled air contains numerous substances, including toxic compounds, and microorganisms. The airway epithelium is central to the defense of the lung against pathogens and particulates that are inhaled from the environment. Other features of G4 EA H1N1 that are characteristic of the 2009 pandemic lineage include high infectivity and transmissibility in a ferret model, says the team.
“Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells and show efficient infectivity and aerosol transmission in ferrets,” says the team.
To determine whether G4 EA H1N1 can infect across species from swine to humans, serological surveillance was conducted to detect the prevalence of virus exposure in swine production workers. A serologic test is a blood test that looks for signs of a previous infection. It detects antibodies, which are proteins in the blood that fight off infection. From 2016 to 2018, a total of 338 serum samples were collected from swine workers in 15 farms. Serum samples (230) from ordinary households were also collected as a population comparison.
According to the authors, the investigation found that the general population, who had little opportunity to contact pigs, lacked antibodies against G4 virus, but swine-exposed adult populations showed elevated seroprevalence, further supporting their hypothesis of G4 virus transmission from pigs to human. The analysis shows that of more than 300 serum samples from workers on pig farms, 10.4% contained antibodies against G4 EA H1N1. The research team says it is of concern that human infection of the G4 virus will further human adaptation and increase the risk of a human pandemic.
“Serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 to 35 years old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses. Thus, the emergent G4 EA H1N1 viruses pose a serious threat to human health,” write authors. “In summary, G4 EA H1N1 viruses possess all the essential hallmarks of being highly adapted to infect humans. Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring in human populations, especially the workers in swine industry, should be urgently implemented,” they warn.