Can Dangerous Bird Flu Virus Fly Between Humans?

Since a new bird flu virus began sickening and killing people in China in March, one of the most pressing questions has been whether the virus, H7N9, would easily spread from human to human, possibly kicking off a global pandemic. Fortunately, no convincing signs of such transmission surfaced, and the outbreak—which led affected Chinese cities to close poultry markets and cull birds—seems to have ground to a halt. But three new studies in ferrets show that the virus can spread in the air between mammals, reawakening worries of human-to-human transmission.


Today, a team led by virologist Hualan Chen of China’s Harbin Veterinary Research Institute reports online in Science that in experiments with ferrets, an H7N9 virus isolated from a human was what the researchers described as “highly transmissible” by respiratory droplets. In the ferret model, widely regarded as one of the best ways to assess human-to-human transmission, researchers intentionally infect animals in one cage and determine whether the virus spreads to others in an adjacent cage. When Chen and colleagues inoculated three ferrets in one cage with H7N9 virus samples from a person who fell ill with the disease in Anhui province, all three ferrets in an adjacent cage became infected, and the viruses isolated from them matched the ones used in the test. The researchers repeated the experiment and found the same outcome. Two other viral samples from different patients spread to only one of three exposed animals, as did one taken from a bird.

Although the ferret model has its limitations, Chen and co-workers conclude that their findings portend future problems. “Currently, implementation of compulsory control measures in H7N9 virus-positive live poultry markets is preventing further human infections; however, the elimination of the H7N9 virus from nature is a huge and long-term challenge,” they write. “Its replication in humans will provide further opportunities for the virus to acquire more mutations and become more virulent and transmissible in the human population.”

But a group at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta that performed a similar experiment with the same Anhui province sample came to a different conclusion. After inoculating two groups of three ferrets, they found that it spread to two of six ferrets in adjacent cages. A different human sample had the same transmission frequency by the respiratory route. As the CDC researchers conclude in the 10 July issue ofNature, the virus “did not transmit readily by respiratory droplets.” In contrast to Chen’s team, they emphasize “that additional virus adaptation in mammals would be required to reach the high-transmissible phenotypes observed by the respiratory droplet route with pandemic and seasonal influenza A viruses.” CDC did not respond to a request for an interview.

A second study published in the same issue of Nature, led by Yoshihiro Kawaoka, a virologist at the University of Wisconsin, Madison, and the University of Tokyo, reported the Anhui sample infected one in three ferrets—the same percentage as CDC found. However, the researchers drew a different conclusion from the CDC group, writing that the respiratory transmission they observed contributes to their assessment that H7N9 viruses pose “a formidable threat to public health.”

Although the Chen group’s findings differ from those of the CDC and Kawaoka teams—and those two labs appear to reach different conclusions about the severity of the threat—virologist Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, notes that the results are not as disparate as they may seem. “H7N9 clearly transmits via aerosol or respiratory droplets in ferrets,” says Fouchier, whose own ferret studies with the H5N1 subtype caused an international uproar when he intentionally made that bird flu virus transmit through the air to help tease out responsible mutations. “In general, human flu viruses transmit in 100% of ferrets, avian in 0%, and this one is in between.”

Nor are the studies likely to be the end of the debate. Statistically, Fouchier says, the experiments included too few ferrets to arrive at conclusions about the likelihood of transmission to exposed animals. “Do you say the glass is half full or half empty?” Fouchier asks. “CDC are the optimists, while the other groups are more pessimistic.” Fortunately, the bottom line at the moment is that H7N9 has not spread efficiently between humans—although a few mutations could tip the scale in the virus’s favor, which warrants close monitoring of how it behaves in birds and us.


Scientists create hybrid flu that can go airborne.


H5N1 virus with genes from H1N1 can spread through the air between mammals.

As the world is transfixed by a new H7N9 bird flu virus spreading through China, a study reminds us that a different avian influenza — H5N1 — still poses a pandemic threat.

A team of scientists in China has created hybrid viruses by mixing genes from H5N1 and the H1N1 strain behind the 2009 swine flu pandemic, and showed that some of the hybrids can spread through the air between guinea pigs. The results are published in Science1.

Flu hybrids can arise naturally when two viral strains infect the same cell and exchange genes. This process, known as reassortment, produced the strains responsible for at least three past flu pandemics, including the one in 2009.

There is no evidence that H5N1 and H1N1 have reassorted naturally yet, but they have many opportunities to do so. The viruses overlap both in their geographical range and in the species they infect, and although H5N1 tends mostly to swap genes in its own lineage, the pandemic H1N1 strain seems to be particularly prone to reassortment.

“If these mammalian-transmissible H5N1 viruses are generated in nature, a pandemic will be highly likely,” says Hualan Chen, a virologist at the Harbin Veterinary Research Institute of the Chinese Academy of Sciences, who led the study.

“It’s remarkable work and clearly shows how the continued circulation of H5N1 strains in Asia and Egypt continues to pose a very real threat for human and animal health,” says Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.

Flu fears

Chen’s results are likely to reignite the controversy that plagued the flu community last year, when two groups found that H5N1 could go airborne if it carried certain mutations in a gene that produced a protein called haemagglutinin (HA)2, 3. Following heated debate over biosecurity issues raised by the work, the flu community instigated a voluntary year-long moratorium on research that would produce further transmissible strains. Chen’s experiments were all finished before the hiatus came into effect, but more work of this nature can be expected now that the moratorium has been lifted.

“I do believe such research is critical to our understanding of influenza,” says Farrar. “But such work, anywhere in the world, needs to be tightly regulated and conducted in the most secure facilities, which are registered and certified to a common international standard.”

Virologists have created H5N1 reassortants before. One study found that H5N1 did not produce transmissible hybrids when it reassorts with a flu strain called H3N24. But in 2011, Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital in Memphis, Tennessee, showed that pandemic H1N1 becomes more virulent if it carries the HA gene from H5N15.

Chen’s team mixed and matched seven gene segments from H5N1 and H1N1 in every possible combination, to create 127 reassortant viruses, all with H5N1’s HA gene. Some of these hybrids could spread through the air between guinea pigs in adjacent cages, as long as they carried either or both of two genes from H1N1 called PA and NS. Two further genes from H1N1, NA and M, promoted airborne transmission to a lesser extent, and another, the NP gene, did so in combination with PA.

“It’s a very extensive paper,” says Schultz-Cherry. “It really shows that it’s more than just the HA. The other proteins are just as important and can drive transmission.” Chen says that health organisations should monitor wild viruses for the gene combinations that her team identified in the latest study. “If those kinds of reassortants are found, we’d need to pay high attention.”

Knowledge gap

It is unclear how the results apply to humans. Guinea pigs have bird-like receptor proteins in their upper airways in addition to mammalian ones, so reassortant viruses might bind in them more easily than they would in humans.

And scientists do not know whether the hybrid viruses are as deadly as the parent H5N1. The hybrids did not kill any of the guinea pigs they spread to, but Chen says that these rodents are not good models for pathogenicity in humans.

There is also a chance that worldwide exposure that already occurred to the pandemic H1N1 strain might actually mitigate the risk of a future pandemic by providing people with some immunity against reassortants with H5N1. In an earlier study, Chen and her colleagues showed that a vaccine made from pandemic H1N1 provided some protection against H5N1 infections in mice6.

“If you take [antibodies] from people who have been vaccinated or naturally infected, will they cross-react with these viruses?” asks Schultz-Cherry. “That’s an important study that would need to be done.”

Ironically, Chen’s team is now too busy reacting to the emerging threat of a different bird flu — H7N9. Research on H5N1 will have to wait.

Source: Nature


FDA Panel Recommends Approval of Adjuvanted Bird Flu (H5N1) Vaccine .

An adjuvanted vaccine against the avian influenza virus (H5N1) has been recommended for approval by an FDA advisory panel, Reuters reported last week.

Another vaccine has already been licensed for H5N1, but the newer vaccine would require much less antigen to be effective because of the presence of the adjuvant. That would make it easier to produce enough doses during an epidemic, according to the report.

Source: Reuters