Molecular change in 1918 pandemic influenza virus stops transmission

Experts at the Centers for Disease Control and Prevention have shown that a molecular change in the 1918 pandemic influenza virus stops its transmission in ferrets that were in close proximity, shedding light on the properties that allowed the 1918 pandemic virus to spread so quickly and potentially providing important clues that could help scientists assess emerging influenza viruses, such as H5N1.

The study, which is published in the Feb. 5 issue of Science, showed that a modest change of two amino acids in the main protein found on the surface of the 1918 virus did not change the virus's ability to cause disease, but stopped respiratory droplet transmission of the virus between ferrets placed in close proximity. The experiments were conducted with ferrets because their reaction to influenza viruses closely mimics how the disease affects humans.

"With this vital research, we are learning more about what may have contributed to the spread and deadliness of the 1918 pandemic," said CDC Director Dr. Julie Gerberding. "By better understanding how this virus spreads, we can be better positioned to slow down or stop the spread of the pandemic virus and hence be better prepared for the next pandemic."

To spread and cause illness, the influenza virus must first bind to host cells found in humans and animals. The Science study suggests that the hemagglutinin (HA), a type of protein found on the surface of influenza viruses, plays an important role in the 1918 virus's ability to transmit from one host to another efficiently. This research suggests that, for an influenza virus to spread efficiently, the virus's HA must prefer attaching to cells that are found predominately in the human upper airway instead of cells found predominately in the gastrointestinal tracts of birds. Other changes may be necessary as well. Current H5N1 viruses prefer attaching to avian cells, suggesting the virus would need to make genetic changes before it could pass easily between humans.

"Work on the 1918 virus is providing clues that are helping us evaluate other influenza viruses with pandemic potential, such as H5N1, that may emerge," said Dr. Terrence Tumpey, lead author of the paper and a CDC senior microbiologist. "Though we still don't know what changes might be necessary for H5N1 to transmit easily among people, it's likely that changes in more than one virus protein would be required for the H5N1 virus to be transmitted among humans."

Influenza pandemics occur when a new strain emerges to which people have little or no immunity. Most experts believe another pandemic will occur, but it is impossible to predict which strain will emerge as the next pandemic strain, when it will occur or how severe it will be.

The 1918 pandemic caused an estimated 675,000 deaths in the United States and up to 50 million worldwide, in the worst pandemic of the past century.

The research was done in collaboration with Mount Sinai School of Medicine and the Southeast Poultry Research Laboratory. All laboratory work with 1918 virus was conducted at CDC in a high containment Biosafety Level 3 laboratory with enhancements, using stringent biosecurity precautions to protect both laboratory workers and the public from exposure to the virus. Currently available antiviral drugs have been shown to be effective against the 1918 influenza virus and similar viruses.

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