The emergence of the 2013 H7N9 and related viruses in China

Abstract

Background: The novel H7N9 influenza A virus first detected in March 2013 has caused more than 130 cases of human infection in China, resulting in 39 deaths. This virus is a reassortant of H7, N9 and H9N2 avian influenza viruses and carries some amino acids linked to mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully understood. Materials and Methods: Following the initial reports of H7N9 influenza infection in humans, field surveillance was conducted during 4th-18th April in Zhejiang, Shandong and Guangdong provinces. Pairs of oropharyngeal and cloacal samples from chickens and other poultry, together with faecal and water samples from live poultry markets (LPMs), farms and wetlands were collected for virus isolation and whole genomic sequencing. H7, N9, N7 and H9N2 archived isolates, obtained during previous influenza surveillance between 2000-2013 in southern China, were also sequenced and phylogenetically analyzed to pinpoint the genesis of the H7N9 and a related H7N7 virus. The infectivity and pathology of H7N9 and H7N7 viruses were tested in a ferret model. Results: Through a combination of active surveillance, screening of virus archives, and evolutionary analyses, we found that H7 viruses have independently transferred from domestic ducks to chickens in China on at least two occasions. Subsequently they reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related but previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at LPMs that appear to be the immediate source of human infections. In ferrets this virus caused a productive infection and pneumonia. Virus was shed via the nasal route and transmitted to physical contact and some airborne-exposed animals. Like the H7N9 virus, the H7N7 virus was also mainly isolated from chickens at LPMs and it could efficiently infect ferrets, be shed via the nasal and rectal routes, and cause severe pneumonia. Conclusions: These findings provide a clear picture showing how the current H7N9 human viruses emerged. Domestic ducks act as primary vectors to acquire and maintain diversified viruses from migratory birds, and facilitate different subtype combinations between H7 and N9 or N7 viruses and interspecies transmissions to chickens. After being introduced, the H7N9 or H7N7 viruses reassorted with enzootic H9N2 viruses and formed the current reassortant H7N9 or H7N7 viruses seen in chickens. This likely led to outbreaks in chickens, resulting in the rapid spread of the novel reassortant H7N9 virus through LPMs, which then became the source of human infections. Whether the H7N9 outbreak lineage will, or has, become enzootic in China needs further investigation. Our results also indicate that H7 viruses pose a broader threat than the current H7N9 virus. Continued prevalence of this family of H7 viruses in poultry could lead to further sporadic human infections, with an ongoing risk that the virus might acquire efficient human-to-human transmissibility.