Pandemic potential of avian influenza A (H7N9) viruses

Abstract

Avian influenza viruses rarely infect humans, but the recently emerged avian H7N9 influenza viruses have caused sporadic infections in humans in China, resulting in 440 confirmed cases with 122 fatalities as of 16 May 2014. In addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with H7N9 viruses. These viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid changes that likely contribute to their ability to infect mammals. In this review, we summarize the characteristic features of the novel H7N9 viruses and assess their pandemic potential.

Keywords: avian influenza H7N9 viruses; pandemic potential; transmission.

Figure 1

Geographic distribution of confirmed human cases of H7N9 influenza virus infection, as of May 16, 2014 (440 total cases). The number of cases in each province is based on data reported by the Centre for Health Protection, Hong Kong PRC SAR (http://www.chp.gov.hk/en/index.html; map revised from a version available at http://www.cidrap.umn.edu/infectious-disease-topics/h7n9-avian-influenza#literature). The darker the green color, the higher the number of cases.

Figure 2

Number of confirmed human cases of H7N9 influenza virus infection in 2013–2014. Number of laboratory-confirmed cases of human infection with H7N9 influenza virus by week of onset of illness (A) and by Chinese provinces by wave (B). Blue and red bars indicate the number of human cases of H7N9 virus infection detected in the first and second waves, respectively. Provinces are categorized into two groups: northern and southern regions of China. (C) Human cases of H7N9 influenza virus infection by age- and gender-groups. Data for graphs (A) and (C) are based on FluTrackers 2013/14 Human Case List of Provincial/Ministry of Health/Government Confirmed Influenza A (H7N9) Cases with Links (http://www.flutrackers.com/forum/showthread.php?t=202713). Number of cases per province in (B) is based on the data shown at the CIDRAP website (http://www.cidrap.umn.edu/sites/default/files/public/downloads/topics/cidrap_h7n9_update_051614_0.pdf).

Figure 2

Number of confirmed human cases of H7N9 influenza virus infection in 2013–2014. Number of laboratory-confirmed cases of human infection with H7N9 influenza virus by week of onset of illness (A) and by Chinese provinces by wave (B). Blue and red bars indicate the number of human cases of H7N9 virus infection detected in the first and second waves, respectively. Provinces are categorized into two groups: northern and southern regions of China. (C) Human cases of H7N9 influenza virus infection by age- and gender-groups. Data for graphs (A) and (C) are based on FluTrackers 2013/14 Human Case List of Provincial/Ministry of Health/Government Confirmed Influenza A (H7N9) Cases with Links (http://www.flutrackers.com/forum/showthread.php?t=202713). Number of cases per province in (B) is based on the data shown at the CIDRAP website (http://www.cidrap.umn.edu/sites/default/files/public/downloads/topics/cidrap_h7n9_update_051614_0.pdf).

Figure 2

Number of confirmed human cases of H7N9 influenza virus infection in 2013–2014. Number of laboratory-confirmed cases of human infection with H7N9 influenza virus by week of onset of illness (A) and by Chinese provinces by wave (B). Blue and red bars indicate the number of human cases of H7N9 virus infection detected in the first and second waves, respectively. Provinces are categorized into two groups: northern and southern regions of China. (C) Human cases of H7N9 influenza virus infection by age- and gender-groups. Data for graphs (A) and (C) are based on FluTrackers 2013/14 Human Case List of Provincial/Ministry of Health/Government Confirmed Influenza A (H7N9) Cases with Links (http://www.flutrackers.com/forum/showthread.php?t=202713). Number of cases per province in (B) is based on the data shown at the CIDRAP website (http://www.cidrap.umn.edu/sites/default/files/public/downloads/topics/cidrap_h7n9_update_051614_0.pdf).

Figure 3

Genesis of H7N9 influenza virus. The novel H7N9 viruses likely resulted from the reassortment of at least four avian influenza A virus strains. The HA gene of the H7N9 viruses is closely related to the Eurasian lineage of avian influenza viruses and to that of the avian H7N3 viruses recently isolated from ducks in Eastern China. The NA gene of the novel H7N9 viruses is closely related to that of avian H2N9 and/or H11N9 influenza viruses isolated from wild migratory birds along the East Asian flyway. The remaining six viral genes likely originated from two distinct subgroups of an H9N2 sub-lineage circulating in poultry in Eastern China. The virus encircled by the dashed line represents a possible precursor of H7N9 avian influenza viruses. Although the H7N9 viruses currently circulating in birds do not encode determinants of mammalian adaptation (i.e., PB2-627K, PB2-701N, or PB2-591K/R and HA-226L/I), such mutations can arise during H7N9 virus replication in humans. This figure was created by modification of a figure in .

Figure 4

Amino acid changes in the HA of viruses recovered from contact ferrets in the human-infecting H7N9 virus groups. Shown is the three-dimensional structure of A/Anhui/1/2003 (H7N9) HA (PDB ID: 4BSE) in complex with human receptor analogues and a close-up view of the globular head. Mutations shown in cyan (i.e., A138S, G186V, and Q226L/I) are known to increase the binding of avian H5 and H7 viruses to human-type receptors. Mutations that emerged in HA of human-infecting H7N9 viruses during replication and/or transmission in ferrets are shown in green (see also Table 2). The human receptor analogue is shown in orange. Images were created with MacPymol [http://www.pymol.org/].