Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus

Abstract

The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.

• avian influenza virus
• genetic evolution
• HPAI A(H5N8)
• migratory waterfowl
• reassortment

We thank Dr Cherisse Guess (St Jude Children's Research Hospital, Memphis, TN, USA) for her excellent editorial assistance. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science (NRF-2007-0054930) and by the Korea Healthcare Technology R&D Project funded by the Ministry of Health (Grant NO A103001). This project was also funded in part (to Richard J Webby and Robert G Webster) with federal funds from the Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400006C) and by the American Lebanese-Syrian Associated Charities.

Note: Supplementary Information for this article can be found on Emerging Microbes and Infections' website (http://www.nature.com/emi/).