Scientists identify a swine flu virus with pandemic potential

"We need to be aware of this risk so that we can start taking measures to prevent spillover now, while it is still in pigs."

In a new study, researchers identify an emergent swine flu virus spreading through China. They claim it has pandemic potential.

The discovery calls for immediate animal and public health precautions and control measures to prevent spillover and a disease outbreak in humans, the study argues.

In light of the widespread devastation wreaked by Covid-19, the idea of another pandemic virus sweeping the globe so soon may sound terrifying. But zoonotic disease experts, who study diseases that transmit between animals and humans, say it’s too early for panic. While it's important to respond to this threat, it is nowhere near the level of Covid-19.

"Right now there is no evidence of human-to-human transmission so we don’t have another human epidemic on our hands," Melinda Rostal, a veterinarian epidemiologist and zoonotic disease expert at EcoHealth Alliance, tells Inverse. Rostal was not involved in the study.

"But they have provided strong evidence through their transmission studies in human cells and ferrets that suggest if human-to-human transmission does start to occur easily we could be facing another large epidemic," Rostal adds. "We need to be aware of this risk so that we can start taking measures to prevent spillover now, while it is still in pigs."

G4 EA H1N1 — The study, published Monday in the journal PNAS, is the result of seven years of data collection, livestock surveys, animal testing, human sampling, and subsequent analysis.

The swine flu virus it identifies, G4 EA H1N1, is a recently emerged viral genotype of swine flu that is circulating in China. The study team writes that it poses a serious threat to human health, adding:

“Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring in human populations, especially the workers in the swine industry, should be urgently implemented."

Taken together, these results suggest that the new swine flu virus could spread quickly in humans and potentially cause a pandemic. Importantly, that possibility has not become a reality yet.

"It is important for people to know and remember that influenza viruses do continue to have the potential cause a pandemic, even as we continue the fight against the coronavirus pandemic," Rostal says. "The results of this study should be acted upon by veterinarians and public health officials in Asia and we should be aware of it."

Pigs and pandemics — Pigs are susceptible to catching and spreading influenza A viruses from birds, humans, and other pigs. This susceptibility means the animals are a key intermediate host, or "mixing vessel," in the development of pandemic influenza viruses.

If a pig is infected with two or more types of viruses at the same time, such as human influenza and swine influenza, the viruses can swap genes in a process called reassortment, Rostal explains. Sometimes this leads to a new strain that can infect people because people do not have immunity to it and there's no vaccine.

The H1N1 “swine flu” virus that caused a pandemic in 2009 involved a virus that had genes from human, swine, and avian influenza viruses. The reassortment occurred in pigs.

"Zoonotic disease experts have been concerned about this type of gene swapping in pigs for some time now - even before the 2009 pandemic," Rostal explains.

Virus-hunting — To track potentially infectious swine flu viruses, between 2011 and 2018, the team collected 29,918 nasal swab samples from pigs in slaughterhouses across 10 provinces in China.

They also took 1,016 nasal swabs or lung samples from pigs showing respiratory symptoms at a veterinary teaching hospital. Forty-three of these pigs were positive for influenza virus.

Overall, the researchers isolated 179 swine flu viruses. Of these viruses, 165 were described as Eurasian Avian-like Influenza A (EA H1N1). This indicated that EA H1N1 is the predominant subtype virus circulating in pig populations in China, the team reports. They analyzed the viruses' genetic makeup and found that genotype 4 (G4) was dominant.

European avian influenza viruses have been circulating since 2001, but according to this analysis, G4 EA H1N1 — the newly identified virus — has been dominant in China since 2016.

To test how G4 EA H1N1 influences the body, the team introduced the virus to human cells and ferrets.

In turn, they found that it exhibits some of the features of the 2001 H1N1 swine flu virus, which sickened over 60,000 million people: It efficiently binds to SAα2,6Gal receptors, replicates efficiently in human airway epithelial cells, and shows high infection and transmissibility in ferrets.

A potential threat — After surveying 300 workers on 15 pig farms, the team also found that 10.4 percent of their blood samples contained antibodies against G4 EA H1N1.

"G4 EA H1N1 viruses possess all the essential hallmarks of being highly adapted to infect humans," the scientists write. "Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring of swine working populations should be promptly implemented."

To date, there have been five human cases of illness linked to this type of virus, the team reports. Two of the patients infected with the virus had neighbors who reared pigs, suggesting that the G4 EA H1N1 virus can transmit from swine to human.

"It is of concern that human infection of G4 virus will further human adaptation and increase the risk of a human pandemic," the team writes.

Based on these findings, scientists should work to strengthen farms in the region's biosecurity, Rostal says.

"While the threat is not imminent, it is important that people working in the pig value chain — such as farmers or sellers — take measures to prevent further transmission of the virus from pigs to people," she says.

Other precautionary measures could include preventing wildlife from coming into contact with these pigs, restricting what people can be in contact with the pigs, and not purchasing and adding new pigs to herds, Rostal says. Veterinary health officials should also start working on a vaccine for use in the pigs to prevent the spread of this particular genotype of the virus, she explains.

For now, it's hard to measure this strain's pandemic potential before there are cases of human-to-human transmission documented, Rostal says. In the meantime, she argues this finding highlights the need to support zoonotic disease monitoring.

"Our health is intricately linked with the health of domestic and wild animals and the environment," Rostal says. "We need to support and trust the scientists that are working hard to track the potential for spillover and pandemics and the veterinary and public health specialists that are working to monitor and prevent these diseases from causing epidemics in people and in animals."

Abstract: Pigs are considered as important hosts or “mixing vessels” for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. 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. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further 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 y to 35 y 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.
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