Emerging bird flu strain is still poorly adapted for infecting humans, study reports

December 5, 2013, The Scripps Research Institute
A study from The Scripps Research Institute showed that H7N9 is still mainly adapted for infecting birds, not humans. This image from the work shows the binding of avian-like glycan receptors (yellow spheres) to the 2013 H7N9 influenza virus hemagglutinin (in ribbon diagram). Credit: Rui Xu, The Scripps Research Institute

Avian influenza virus H7N9, which killed several dozen people in China earlier this year, has not yet acquired the changes needed to infect humans easily, according to a new study by scientists at The Scripps Research Institute (TSRI). In contrast to some initial studies that had suggested that H7N9 poses an imminent risk of a global pandemic, the new research found, based on analyses of virus samples from the Chinese outbreak, that H7N9 is still mainly adapted for infecting birds, not humans.

"Luckily, H7N9 viruses just don't yet seem well adapted for binding to human receptors," said Ian A. Wilson, the Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI.

"Because publications to date have implied that H7N9 has adapted to human receptors, we felt we should make a clear statement about this," said James C. Paulson, chair of TSRI's Department of Cell and Molecular Biology.

The Wilson and Paulson laboratories collaborated on the study, which is reported in the December 6, 2013 issue of the journal Science.

A Worrisome Outbreak

H7N9 flu viruses infect birds, apparently causing them few or no symptoms. Until this year these strains had never been reported in humans. However, starting in February in two urban areas of eastern China, dozens of people began to come down with H7N9 flu. Most became severely ill. By the end of May, when the outbreak had mostly subsided, there were 132 laboratory-confirmed human cases and 37 deaths—a nearly 30% case-fatality rate.

The outbreak understandably alarmed public health officials, and across the globe dozens of laboratories began studying H7N9 isolates from infected patients. The big question was whether these strains were capable of spreading only in a limited, sporadic way from birds to humans—many of the cases were linked to poultry exposure—or if they had truly "jumped the species barrier." If the latter were true, and H7N9 could now spread from human to human, the Chinese outbreak might be the start of a .

Some prominent early studies came to worrisome conclusions. For example, most of the H7N9 isolates from the outbreak turned out to have acquired a notorious flu-virus mutation that substitutes the amino acid leucine for glutamine in the part of the virus that grabs receptors on host cells. The same mutation, in other subtypes, was apparently a key enabler of pandemics that killed an estimated one million people worldwide in 1968-69 (the "Hong Kong flu") and two million during 1957-58 (the "Asian flu"). Initial studies of the new H7N9 isolates in mice, ferrets and monkeys also suggested that they had at least a limited ability to spread among mammals.

Answering Critical Questions

Paulson's and Wilson's laboratories, long experienced in flu virus and immunity research, were among the many that mobilized to try to answer the crucial question of H7N9's transmissibility among humans. They quickly decided to collaborate. Paulson's laboratory evaluated H7N9's ability to bind the sialylated sugar receptors to which normally attach on host cells. Wilson's laboratory used X-ray crystallography to determine the atomic structures of the H7N9 hemagglutinin protein bound to these sialic acid receptor molecules.

Paulson's team—including postdoctoral fellows Robert P. de Vries and Corwin M. Nycholat and Research Assistant Ryan McBride—tested the ability of the virus's hemagglutinin (HA) protein, to bind to different human and avian receptor variants. These tests showed clearly that the isolate tested (A/Shanghai/2/2013 or "Sh2") still has a strong preference for avian-type receptors and binds human-type receptor variants only weakly.

In Wilson's laboratory, postdoctoral fellow Rui Xu, the study's first author, along with Staff Scientist Xueyong Zhu and Research Assistant Wenli Yu, performed X-ray crystallography studies of the Sh2 HA protein bound to several avian- and human-type receptors. The latter, provided by Paulson's laboratory, were more accurate versions of these receptors than any that had been used in previous H7N9 structural analyses.

The new data highlighted the looseness of the contacts that Sh2 HA makes with human-type receptors, in contrast to the snug couplings it makes with certain avian-type receptors.

Thus, despite hints that it had begun to adapt to human hosts rather than its natural bird hosts, H7N9 does not appear to pose an imminent threat of a human pandemic. "These results suggest that we should continue to observe H7N9 and see if it undergoes any changes that make it more likely to spread in the human population," said Wilson. Paulson added, "If it does evolve a true human-type receptor specificity, it could potentially spread among humans much better than it does now."

Explore further: Studies showing how bird flu viruses could adapt to humans offer surveillance and vaccine strategies

More information: "Preferential Recognition of Avian-Like Receptors in Human Influenza A H7N9 Viruses," Science, 2013.

Related Stories

Studies showing how bird flu viruses could adapt to humans offer surveillance and vaccine strategies

June 6, 2013
Bird flu viruses are potentially highly lethal and pose a global threat, but relatively little is known about why certain strains spread more easily to humans than others. Two studies published today in the journal Cell identify ...

Study puts troubling traits of H7N9 avian flu virus on display

July 10, 2013
The emerging H7N9 avian influenza virus responsible for at least 37 deaths in China has qualities that could potentially spark a global outbreak of flu, according to a new study published today (July 10, 2013) in the journal ...

Bird flu in live poultry markets are the source of viruses causing human infections

May 13, 2013
On 31 March 2013, the Chinese National Health and Family Planning Commission announced human cases of novel H7N9 influenza virus infections. A group of scientists, led by Professor Chen Hualan of the Harbin Veterinary Research ...

Hong Kong confirms first human case of H7N9 bird flu (Update)

December 2, 2013
Hong Kong on Monday confirmed its first human case of the deadly H7N9 bird flu, according to a report, in the latest sign of the virus spreading beyond mainland China.

Source identification of H7N9 influenza virus causing human infections

April 25, 2013
In March 2013, a novel H7N9 influenza virus was identified in China as the etiological agent of a flu-like disease in humans, resulting in some deaths. A group of scientists, led by Professor Chen Hualan (National Avian Influenza ...

Food additive may prevent spread of deadly new avian flu

October 23, 2013
A common food additive can block a deadly new strain of avian influenza virus from infecting healthy cells, report researchers at the University of Illinois at Chicago College of Medicine in the online journal, PLOS ONE.

Recommended for you

Onions could hold key to fighting antibiotic resistance

January 22, 2018
A type of onion could help the fight against antibiotic resistance in cases of tuberculosis, a UCL and Birkbeck-led study suggests.

New long-acting approach for malaria therapy developed

January 22, 2018
A new study, published in Nature Communications, conducted by the University of Liverpool and the Johns Hopkins University School of Medicine highlights a new 'long acting' medicine for the prevention of malaria.

Virus shown to be likely cause of mystery polio-like illness

January 22, 2018
A major review by UNSW researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.