The 1918 H1N1 Spanish Influenza pandemic was the most severe pandemic in modern history. Unlike more recent pandemics, most of the 1918 H1N1 virus’ genome was derived directly from an avian influenza virus. Recent avian-origin H5 A/goose/Guangdong/1/1996 (GsGd) and Asian H7N9 viruses have caused several hundred human infections with high mortality rates. While these viruses have not spread beyond infected individuals, if they evolve the ability to transmit efficiently from person-to-person, specifically via the airborne route, they will initiate a pandemic. Therefore, this review examines H5 GsGd and Asian H7N9 viruses that have caused recent zoonotic infections with a focus on viral properties that support airborne transmission. Several GsGd H5 and Asian H7N9 viruses display molecular changes that potentiate transmission and/or exhibit ability for limited transmission between ferrets. However, the hemagglutinin of these viruses is unstable; this likely represents the most significant obstacle to the emergence of a virus capable of efficient airborne transmission. Given the global disease burden of an influenza pandemic, continued surveillance and pandemic preparedness efforts against H5 GsGd and Asian lineage H7N9 viruses are warranted.
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