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Three Mutations Could Help Bird Flu Spread Among Humans

Scientists have identified 3 mutations that, if they occurred at the same time, could allow the avian influenza strain H7N9 to spread among humans.
Robert P. de Vries, PhD, from Utrecht University, The Netherlands, and Wenjie Peng, PhD, from The Scripps Research Institute, La Jolla, California, and colleagues published the results of their study online recently in PLOS Pathogens.
H7N9 is a subtype of avian influenza virus that usually infects birds. But, it is also a serious threat to human health, and has already crossed the species barrier into humans, causing hundreds of human infections and deaths. These cases have predominantly involved individuals exposed to H7N9-infected birds at poultry markets.
However, in an interview with Contagion®, corresponding author James C. Paulson, PhD, professor and co-chair in the Department of Molecular Medicine at The Scripps Research Institute, explained that although the H7N9 virus subtype is infecting humans, it cannot easily spread between them.
Professor Paulson said that the avian virus cannot attach to cells in the lungs of humans. He noted that the virus has a protein called hemagglutinin (HA) that coats its surface and helps the virus bind to receptors on the cells that it infects. According to Professor Paulson, the amino acid structures of HA on human influenza viruses allow the viruses to recognize and bind to the receptors on cells in the human airway. In contrast, the HA in avian H7N9 influenza virus has a different structure and cannot effectively attach to cells in the human respiratory tract.
To effectively spread among humans, the avian virus thus needs to develop specificity to receptors in the human airway.
Yet, although avian H7N9 influenza virus is currently unable to effectively spread between humans, scientists remain concerned that the virus might one day mutate into a form that could easily transmit in this way.
Professor Paulson and colleagues therefore conducted a study to investigate which mutations would allow the virus to attach to human cells. 
The researchers analyzed mutations in the H7N9 virus, focusing on a gene that codes for one HA protein known as H7. They investigated changes that would alter the amino acid structure of H7 HA, allowing it to switch to recognize receptors in the human airway.
The researchers found that three specific amino acid mutations in H7 HA allowed the virus to more easily bind to human airway cells in the laboratory. These subtle changes in the protein’s structure thus produced virus strains that switched their target from bird cells to human cells.
As to whether the virus could potentially make this switch in nature, Professor Paulson emphasized that he “took comfort in the fact that the switch required 3 amino acids.”
He went on to note that thousands of genomic sequences of influenza virus are isolated each year from humans and birds. And, although some reported cases have involved one of the three mutations, Professor Paulson stressed that none have involved all three mutations together.
Professor Paulson explained that his team was unable to introduce these mutations into actual H7N9 viruses to determine whether the changes would facilitate aerosol transmission of the virus in laboratory animals. This is because of a moratorium on gain-of-function research, he said. This moratorium currently prevents researchers in the United States from conducting studies that involve mutating viruses in such a way that could make them more likely to transmit in humans.
However, the researchers would like to conduct a study in which they introduce the mutated avian influenza HA gene into a weakened laboratory strain of human influenza virus, and examine how this mutation affects transmission of the virus in laboratory animals. “For this, we would collaborate with a team at a biosafety level 3 facility,” Professor Paulson concluded.
Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.
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