The next wave of bird flu could be worse than ever

Test finds mutated strain of H7N9 can pass between lab animals through the air

market in Dongguan, China

POULTRY PROBLEMS  So far, most cases of human H7N9 infection have come from exposure to birds, often in live poultry markets. Here, epidemiologists collect samples at a market in Dongguan, China, in 2014.

CDC/Shuqing Zhao, China

A new version of the H7N9 avian influenza virus might be able to cause widespread infection and should be closely monitored, scientists say, although it currently doesn’t spread easily between people.

Researchers isolated the virus from a fatal human case and tested it and two genetically modified versions in ferrets, which are susceptible to both human and bird flu viruses. The tested viruses can spread to other ferrets through airborne fluid droplets like those released by a cough or a sneeze, sometimes turning deadly, researchers report October 19 in Cell Host and Microbe.

“This is an extremely well-done study,” says John Lednicky, a virologist at the University of Florida in Gainesville who wasn’t part of the research. It links the behavior of the virus to its genetics — a key to understanding what makes a given virus dangerous and to monitoring its spread through a population.  

Various strains of H7N9 influenza have been circulating in China since 2013. The virus has caused 1,564 reported human infections to date in several epidemic waves (SN: 3/22/14, p. 32), and 39 percent of people infected have died. Most were infected with a version of the virus that doesn’t make birds particularly sick. But a recent genetic mutation has made H7N9 better able to replicate in birds and sicken them — which might affect the way it behaves in humans, too.

Yoshihiro Kawaoka, a pathologist at the University of Wisconsin–Madison, and colleagues isolated H7N9 virus particles from someone who was infected with, and died from, this newer, highly pathogenic version of the H7N9 virus in 2016. A genetic analysis revealed that the sample actually contained two different varieties of H7N9. A small genetic change had made one of those varieties resistant to Tamiflu, the leading anti-viral drug used against flu. (The patient had been treated with the drug while alive.)

Using the patient’s virus as a starting point, Kawaoka and his colleagues engineered two different strains of highly pathogenic H7N9, one that was Tamiflu-resistant and one that wasn’t. Then the researchers looked at the way those strains behaved in mice, ferrets and monkeys compared with two other types of H7N9: a less infectious version that first emerged in 2013 and the one isolated from the patient in 2016.

Ferrets have the same kind of proteins that the flu latches onto in humans. That makes ferrets good proxy for the way flu might behave inside the human body, says Kawaoka.

The 2016 virus and the new Tamiflu-sensitive strain made both ferrets and mice sicker, the researchers found. Those strains were also more effective at replicating inside the animals than the 2013 virus. (The Tamiflu-resistant strain wasn’t as successful.) Overall, that suggests that as the virus has gotten worse for birds, it also might be becoming more dangerous in humans.

In another experiment, the researchers paired sick ferrets with healthy ones, separating the animals with a barrier that allowed air to pass between the cages. Each sick ferret had been infected with one of the four virus strains previously tested. Though the ferrets had no direct contact with each other, all of the highly pathogenic virus strains (the 2016 sample and the genetically tweaked strains) spread through the air via respiratory droplets to infect ferrets in neighboring cages. The strain engineered to be sensitive to Tamiflu, for example, infected three of the four ferrets housed next to sick animals; two of the infected animals died.

The Tamiflu-resistant strain didn’t kill any of the ferrets that caught it. It also responded to a different type of flu treatment, called a polymerase inhibitor. (This treatment isn’t currently available in the United States, Kawaoka says, though polymerase inhibitors have been tested in clinical trials.)

Since flu viruses mutate quickly and unpredictably, it’s impossible to forecast if and when an outbreak will spread between countries or continents. H7N9 has many qualities that put it on a pandemic watch list — its ability to spread to through the air, to make infected animals very sick, and the fact that some varieties are drug resistant. But there’s no cause for panic right now, Kawaoka says. The virus is still confined to China, in large part because it doesn’t currently spread very well between people.

The study didn’t address whether smaller aerosolized droplets from coughs and sneezes could spread the virus longer distances, Lednicky says — a characteristic that would make the virus more transmissible. The large droplets that infected the ferrets in the study can travel only about a meter, limiting the virus’ spread.

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