What the world does not need now is a pandemic in addition to a pandemic. Therefore, a new finding that Chinese pigs are increasingly infected with a strain of influenza that has the potential to jump into humans has made infectious disease researchers around the world realize it. Robert Webster, an influenza researcher who recently retired from St. Jude Children's Research Hospital, says it's a "guessing game" about whether this strain will mutate to spread easily between humans, which he has not yet done. "We just don't know that a pandemic will happen until the damn thing happens," says Webster, noting that China has the world's largest pig population. "Will this one do it? God knows."
When multiple strains of influenza viruses infect the same pig, they can easily switch genes, a process known as "rearrangement." The new study, published today in the procedures of the National Academy of Sciences, focuses on an influenza virus called G4. The virus is a unique combination of three lineages: one similar to the strains found in European and Asian birds, the H1N1 strain that caused the 2009 pandemic, and a North American H1N1 that has genes from the avian, human, and swine flu viruses.
The G4 variant is of particular concern because its core is an avian influenza virus, to which humans have no immunity, with fragments of mixed mammalian strains. "Based on the data presented, it appears that this is a swine influenza virus that is about to emerge in humans," says Edward Holmes, an evolutionary biologist at the University of Sydney who studies pathogens. "Clearly this situation needs to be closely monitored."
As part of a project to identify possible strains of pandemic influenza, a team led by Liu Jinhua of the China Agricultural University (CAU) analyzed nearly 30,000 nasal swabs taken from pigs in slaughterhouses in 10 Chinese provinces, and another 1,000 pig swabs with respiratory symptoms seen in his school's veterinary teaching hospital. The swabs, collected between 2011 and 2018, produced 179 swine flu viruses, the vast majority of which were G4 or one of the other five G strains of the Eurasian avian lineage. "The G4 virus has shown a sharp increase since 2016, and is the predominant genotype in circulation in pigs detected in at least 10 provinces," they write.
Sun Honglei, the first author of the article, says that the inclusion of G4 genes from the 2009 H1N1 pandemic "may promote adaptation of the virus" leading to human-to-human transmission. Therefore, "surveillance needs to be strengthened" for Chinese pigs to detect influenza viruses, says Sun, also at the CAU.
Influenza viruses often jump from pigs to humans, but most are not transmitted from human to human. Two cases of human G4 infections have been documented, and both were dead-end infections that were not transmitted to others. "The probability that this particular variant will cause a pandemic is low," says Martha Nelson, an evolutionary biologist at the Fogarty International Center at the US National Institutes who studies swine influenza viruses in the United States and their spread to humans. But Nelson notes that no one knew about the pandemic H1N1 strain, which jumped from pigs to people, until the first human cases appeared in 2009. "Influenza can surprise us," says Nelson. "And there is a risk that we neglect influenza and other threats at this time" from COVID-19.
The new study offers just a small glimpse at swine flu strains in China, which has 500 million pigs. While Nelson believes that G4 dominance in his analysis is an interesting finding, he says it's difficult to know if its spread is a growing problem, given the relatively small sample size. "It really isn't getting a good snapshot of what's dominant in pigs in China," he adds, stressing the need for more samples in Chinese pigs.
In the document, Sun and his colleagues, including George Gao, chief of the Chinese Center for Disease Control and Prevention, describe laboratory plaque studies showing how G4s have become adept at infecting and copying into epithelial cells. of the human respiratory tract. Viruses are also easily infected and transmitted between ferrets, a popular animal model used to study human influenza. The researchers found antibodies against the G4 strain in 4.4% of the 230 people studied in a household survey, and the rate more than doubled in pig workers.
In addition to stepping up surveillance, Sun says it makes sense to develop a G4 vaccine for both pigs and humans. Webster says that at least the seed stock for making a human vaccine, variants of a rapidly growing strain in eggs used to make a flu shot, should be produced now. "Making the seed stock is not a big problem, and we should have it done," says Webster.
China rarely uses influenza vaccines in pigs. Nelson says US farms commonly do, but the vaccine has little effect because it is often outdated and does not match circulating strains.
Ideally, Nelson says, we would produce a human G4 vaccine and have it in stock, but that is a complicated process that requires substantial funding. "We have to be on the lookout for other infectious disease threats, even while COVID is happening because the viruses have no interest in knowing if we are already having another pandemic," says Nelson.
