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Change Allows Influenza Virus to Spread in Respiratory Droplets

Avian H9N2 influenza hasn't garnered the attention of H5N1, but it, too, might have the potential to cause a pandemic flu. A new study shows that H9N2 can fairly easily gain the ability to transmit in respiratory droplets, like that from a sneeze. Insights from the study will have profound implications for pandemic flu preparation.

Avian influenza viruses primarily infect birds now, but these viruses constantly change, or mutate. Future mutations might render them capable of causing a worldwide flu pandemic. Researchers have focused much attention on H5N1 because of the human deaths it's caused. But researchers don't have a very good understanding of how new pandemic viruses emerge.

H9N2 has become endemic in poultry throughout Europe and Asia within the past few years. It's also occasionally infected people. To date, H9N2 infections have typically caused symptoms similar to a seasonal flu, making them likely to escape the attention of public health officials. Given ample opportunity to circulate, exchange genetic material with other viruses and improve its ability to infect and spread, one of these viruses could unexpectedly spark a pandemic.

Dr. Daniel R. Perez at the University of Maryland and his colleagues have been studying avian H9N2 viruses in ferrets, which are considered the gold standard influenza animal model. The team previously showed when an avian H9N2 virus and a human virus exchanged genetic material, a resulting "reassortant" virus could replicate and transmit more effectively than the parent H9N2 virus. This virus however, didn't transmit through respiratory droplets, the main mode of influenza transmission in ferrets.

The researchers set out to determine whether the reassortant virus could gain this ability. Their investigation, funded by NIH's National Institute of Allergy and Infectious Diseases (NIAID), the Centers for Disease Control and Prevention and the U.S. Department of Agriculture, appeared in the online edition of Proceedings of the National Academy of Sciences on April 20, 2009.

The researchers infected ferrets through their noses, then collected nasal washes 3 days later, pooled the washes and used them to infect other ferrets. After passing the virus through ferrets 10 times, the scientists discovered that the viruses spread to other ferrets through respiratory droplets by 4 days after infection.

Sequencing of the viruses revealed that 3 amino acid changes on virus surface proteins—2 in the hemaglutinin protein (the "H" of the virus's name) and 1 in the neuraminidase protein (the "N")—were responsible for enabling respiratory droplet transmission. Importantly, one of these changes is located near a part of the HA protein that scientists have been targeting for potential vaccines. Antibodies that recognize this region in other H9N2 viruses, the researchers found, reacted poorly against the new reassortant virus.

This study suggests that avian H9N2 viruses require little adaptation to gain the ability to spread through respiratory droplets. The crucial changes the researchers pinpointed may prompt a rethinking of how to develop vaccines for a potential pandemic.

—Harrison Wein, Ph.D.