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Pigeon paramyxovirus type 1 (PPMV‐1) is an antigenic variant of Newcastle disease virus (NDV) which is mainly associated with infections of pigeons and has the potential to result in disease in chickens. In this study, we characterised 21 PPMV‐1 isolates from diseased pigeons in China during 2007–2019. Phylogenetic analysis revealed that all isolates belonged to genotype VI. Among them, most isolates belonged to sub‐genotype VI.2.1.1.2.2, suggesting that VI.2.1.1.2.2 has become a prevalent genotype in pigeons in China. The results showed that all PPMV‐1 isolates were mesogenic in nature according to the mean death time (MDT) and intracerebral pathogenicity index (ICPI). In vitro and in vivo studies demonstrated that two genetically closely related isolates (Pi‐11 and Pi‐10) both of which belonged to sub‐genotype VI.2.1.1.2.2 had similar replication kinetics in cells derived from pigeons, while the replication titre of Pi‐11 was significantly higher than that of Pi‐10 in cells derived from chickens. Pi‐11 and Pi‐10 could contribute to morbidity and mortality in pigeons. Remarkably, although the two viruses resulted in no apparent disease symptom in chickens, Pi‐11 could cause more severe histopathological lesions and had a stronger replication ability in chickens compared to Pi‐10. Moreover, chickens infected with Pi‐11 had higher shedding efficiency than chickens infected with Pi‐10. Additionally, several mutations within important functional regions of the fusion (F) and haemagglutinin‐neuraminidase (HN) proteins might be associated with different pathogenicity of the two viruses in chickens. Collectively, these results indicated that the Pi‐11‐like virus of pigeon origin has the potential to induce severe outbreaks in chicken flocks. These findings will help us better understand the epidemiology and evolution of PPMV‐1 in China and serve as a foundation for the further investigation of the mechanism underlying the pathogenic difference of PPMV‐1 isolates in chickens. [ABSTRACT FROM AUTHOR]

Pre‐existing immunity against the conserved haemagglutinin (HA) stalk underlies the elicitation of cross‐group antibody induced by natural H7N9 virus infection and immunization in humans. However, whether broadly reactive antibodies can be induced by H7N9 infection and immunization in the absence of pre‐existing stalk‐specific immunity is unclear. In this study, antibody response induced by H7N9 virus infection and immunization with inactivated and viral‐vectored H7N9 vaccines in naïve chickens was analysed. The results showed that H7N9 infection and immunization with inactivated vaccine resulted in potent induction of haemagglutination‐inhibition (HI), virus neutralization (VN) and HA‐binding antibodies, whereas Newcastle disease virus (NDV)‐vectored H7N9 vaccine induced marginal HI and VN titres but high levels of HA‐binding antibody. In addition, H7N9 infection and immunization induced stalk‐specific antibodies in naïve chickens and these antibodies recognized different epitopes in the stalk. Virus infection and immunization with inactivated vaccine elicited antibodies cross‐reactive with both group 1 and group 2 HAs, while antibodies induced by NDV‐H7N9 vaccination showed a narrower cross‐reactivity within group 2. Moreover, only homologous neutralizing activity of the sera against H7N9 virus was observed, and cross‐binding antibodies did not show heterosubtypic neutralizing activity. Our results indicated that cross‐group binding but non‐neutralizing antibodies primarily targeting the stalk can be induced by natural H7N9 infection and immunization with inactivated vaccine in naïve chickens. This suggests that at least in a naïve chicken model, pre‐existing stalk‐specific immunity is not required for induction of broadly reactive antibodies. Additionally, H7N9‐based immunogens may be explored as vaccine candidates or as a prime component to induce broadly protective influenza immunity. [ABSTRACT FROM AUTHOR]

Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1‐like M and PB2 genes for the earlier F/98‐like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1‐like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared with the F/98‐like counterpart, while the G1‐like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1‐like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses. [ABSTRACT FROM AUTHOR]

Before 2013, zoonotic influenza infections were dominated by H5N1 viruses in China. However, the emergence of the H7N9 viruses in early 2013 changed this dominance greatly, and more than 1,600 laboratory‐confirmed human cases of H7N9 infections have been reported since then. To understand the underlying mechanism of the emergence of the fifth epidemic wave that shows an unexpected sharp increase, we systematically investigated the biological characteristics of the highly pathogenic (HP) and low‐pathogenic (LP) H7N9 AIVs during this period. We first systematically analysed the haemagglutination assay gene of all the isolates available from the website and found that the HP and LP viruses differed a little in the well‐established receptor binding sites and in other potentially important sites. Phylogenetic analysis showed that both the HP and LP viruses belong to the branch of the Yangtze River Delta, whereas they diverged to different small branches. To further compare the biological variations in the HP and LP viruses, we selected six HP and six LP strains for in‐depth analysis, including receptor binding characteristics, thermal stability, viral replication and virulence in mice. The three major findings of this study were as follows: (a) Other potential site/sites may affect the receptor binding property of the H7N9 viruses; (b) the HP viruses displayed a higher thermostability than did the LP viruses, quite consistent with the epidemiological data during the summer period; and (c) one‐third of the HP viruses were moderately pathogenic in mice, whereas all the LP viruses were nonpathogenic in this animal model. However, the LP viruses replicated more efficiently in the mouse lung and can spread to the extrarespiratory organs (spleen, kidney and brain). Taken together, our results suggest that both the HP and LP H7N9 viruses can pose a potential threat to public health, highlighting the importance of the continual surveillance of the H7N9 AIVs. [ABSTRACT FROM AUTHOR]