Welcome to the course. In this session, we’re going to talk about emergence of the H7N9 influenza A virus in China. In the past decades, China sees the emergence of many notorious viruses. These include the highly pathogenic H5N1, the multiple lineages of H9N2, the very recent H7N9, and some sporadic human infection cases caused by other subtypes of influenza viruses. You may wonder why China and why influenza virus is involved in these events again and again; and how did this happen. Here I would like to take the H7N9 incidence as example to illustrate the following learning objectives: Number one, ecology and interspecies transmission of the influenza A virus. Number two, origin and evolutionary pathways of the novel avian influenza viruses. Number three, management and disease control measures at the human and animal interface. China is home to the world’s biggest human population. It also hosts the largest numbers of domestic ducks, geese, chickens, minor poultry, and pigs. Frequent interactions between all these species and with wildlife occur all the time. This has provided ideal interface for the virus transmissions between hosts and the introduction of new viral gene components. With the rapid economic growth and increasing wealth, farming and trading practices in China have been greatly changed by industrialization and globalization in the quest for great production and better quality food sources. Long-distance transportation of poultry and livestock from other countries or from the remote regions are very common nowadays. When the live animals from different sources and of different species gather at the wholesale markets or distribution centers pathogens also get the chance to congregate. Exchanges of genetic materials generate new variants; introduction to the alien host species drives the natural selection and adaptations, and proliferation in a bigger and more diverse population results in the amplification of the infectious agents. When the infected live animals are redistributed to live poultry markets located almost in every city in this country, viruses carried by them also get disseminated to these retail outlets. These are where human beings become extensively exposed to the exotic viruses. As a segmented single stranded RNA virus, influenza virus adopts various evolutionary strategies such as reassortment, mutation and more rarely, recombination. Interspecies transmission and reassortment are usually followed by adaptive mutations and evolution. In March 2013, the Chinese government announced the occurrence of human infections with a novel subtype of influenza virus, the H7N9. This virus has caused more than 400 human cases within a year, and has a fatality of about 1/3. Phylogenetic analysis found this H7N9 virus to be a reassortment between the H7, N9, and H9N2 viruses. This phylogenetic tree clearly shows how the H7 gene was introduced into poultry in China and how they reassorted to become the infectious H7N9 virus to humans. Influenza viruses of H7 subtype are not rare in migratory birds. In the last decade, H7 viruses were repeatedly introduced from the migratory birds to the domestic ducks, occurring four to five times in our surveillance area in southern China. Among all these introductions, one virus that occurred in 2010, became established in domestic ducks and formed a virus lineage, which was called the Zhejiang-5 lineage. This virus lineage was detected in Fujian, Jiangxi, Zhejiang and Guangdong provinces before the outbreak of H7N9 human infections. The prevalent duck H7 viruses could be occasionally interspecies transmitted to chickens, and subsequently reassorted with viruses enzootic in chickens and caused outbreaks in these birds. In year 2013, almost at the same time when the H7N9 caused human infections in eastern China, an H7N7 virus highly related to the H7N9 emerged in the same area. These two viruses shared the same origins of all gene segments except for the NA surface gene. Our phylogenetic analysis suggested that these two H7 viruses were generated by two independent interspecies transmissions from ducks to chickens, and serial independent reassortment with the enzootic H9N2 viruses to get their internal genes. Similarly, the NA genes of the highly related H7N9 and H7N7 viruses were both derived from viruses carried by the aquatic migratory birds along the Eurasian flyway, and later passed on by the domestic ducks to the chickens. Sequential reassortment with the enzootic H9N2 viruses in chickens generated a variety of H7N9 and H7N7 viruses with the potential to infect humans. Therefore, in this process, domestic ducks played a key role as the intermediate hosts in the genesis of the H7N9 virus. First, the farmed ducks, as part of the nature reservoirs of the influenza A viruses, acquired and maintained the highly diverse influenza viruses derived from migratory birds, and they can facilitate the generation of different subtype combinations by reassortment. Influenza A viruses carried by the ducks usually caused no disease symptoms but can be shed and maintained for quite a long time. When the duck carriers have a chance to meet with the chickens, they can pass the different reassorted viruses to this land-based poultry and allow further reassortment to take place in the new host, with the enzootic viruses well established in chickens. As chickens are the major terrestrial poultry species most commonly seen in the live poultry markets, they become the amplifier for the newly generated viruses and the direct source of human infections. In summary, the ecology and farming practice in China facilitate the genesis of emerging infectious disease agents, especially avian influenza viruses. Viruses with the potential to infect humans, such as the H7N9 and the related H7N7 viruses, can be generated through interspecies transmission and multiple reassortments in the ducks and the chickens. Chickens at the live-poultry markets are the major source of human infections, and long-distance transportation and trading are responsible for the virus dissemination across different geographic regions. The H10N8 virus that caused three human infection cases last Winter in Jiangxi province, also followed exactly the same evolutionary pathways and interspecies transmission patterns. To control H7N9 and other emerging avian influenza viruses ultimately, it is necessary to reconsider the management of current agriculture and trading practices, especially control measures applied at the live poultry markets in urban areas. Long-term influenza surveillance remains essential for early warnings of novel reassortant viruses and interspecies transmission events.
