Dataset Information

Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses.

ABSTRACT: Clade 2.3.4.4 highly pathogenic avian influenza viruses (H5Nx) have spread from Asia to other parts of the world. Since 2014, human infections with clade 2.3.4.4 highly pathogenic avian influenza H5N6 viruses have been continuously reported in China. To investigate the genesis of the virus, we analyzed 123 H5 or N6 environmental viruses sampled from live-poultry markets or farms from 2012 to 2015 in Mainland China. Our results indicated that clade 2.3.4.4 H5N2/N6/N8 viruses shared the same hemagglutinin gene as originated in early 2009. From 2012 to 2015, the genesis of highly pathogenic avian influenza H5N6 viruses occurred via two independent pathways. Three major reassortant H5N6 viruses (reassortants A, B, and C) were generated. Internal genes of reassortant A and B viruses and reassortant C viruses derived from clade 2.3.2.1c H5N1 and H9N2 viruses, respectively. Many mammalian adaption mutations and antigenic variations were detected among the three reassortant viruses. Considering their wide circulation and dynamic reassortment in poultry, we highly recommend close monitoring of the viruses in poultry and humans. IMPORTANCE Since 2014, clade 2.3.4.4 highly pathogenic avian influenza (H5Nx) viruses have caused many outbreaks in both wild and domestic birds globally. Severe human cases with novel H5N6 viruses in this group were also reported in China in 2014 and 2015. To investigate the genesis of the genetic diversity of these H5N6 viruses, we sequenced 123 H5 or N6 environmental viruses sampled from 2012 to 2015 in China. Sequence analysis indicated that three major reassortants of these H5N6 viruses had been generated by two independent evolutionary pathways. The H5N6 reassortant viruses had been detected in most provinces of southern China and neighboring countries. Considering the mammalian adaption mutations and antigenic variation detected, the spread of these viruses should be monitored carefully due to their pandemic potential.

SUBMITTER: Yang L

PROVIDER: S-EPMC5309950 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:From 2013 onwards, the spread of novel H5N6 highly pathogenic avian influenza (HPAI) viruses in China has posed great threats to not only poultry industry but also human health. Since late-2016 in particular, frequent outbreaks of clade 2.3.4.4 H5N6 HPAI viruses among wild birds have promoted viral dissemination in South Korea, Japan, and European countries. In response to those trends, we conducted molecular genetic analysis of global clade 2.3.4.4 H5N6 viruses in order to characterize spatio-temporal patterns of viral diffusion and genetic diversity among wild birds and poultry. The clade 2.3.4.4 H5N6 viruses were classified into three groups (Group B, C, and D). During the cocirculation of Group C/D H5N6 viruses from 2013 to 2017, viral movements occurred between close or adjacent regions of China, Vietnam, South Korea, and Japan. In addition, viral migration rates from Guangdong and Hunan to multiple adjacent provinces seemed to have been highly supported by transmission routes (Bayes factors >100), suggesting that southern China was an epicenter for the spread of H5N6 viruses in poultry during that period. Since the introduction of H5N6 viruses originating in wild birds in late-2016, evolving H5N6 viruses have lost most previous genotypes (e.g. G1, G2, and G1.2), whereas some prevailing genotypes (e.g. G1.1, G1.1.b, and G3) in aquatic birds have been dominated, and in particular, the effective population size of H5N6 originating in wild birds dramatically increased; however, the population size of poultry-origin H5N6 viruses declined during the same period, indicating that wild bird migration might accelerate the genetic diversity of H5N6 viruses. Phylogeographic approaches revealed that two independent paths of H5N6 viruses into South Korea and Japan from 2016 to 2018 and provided evidence of Group B and Group C H5N6 viruses were originated from Europe and China, respectively, as regions located in the East Asia-Australian migration flyway, which accelerated the genetic variability and dissemination. Altogether, our study provides insights to examine time of origin, evolutionary rate, diversification patterns, and phylogeographical approach of global clade 2.3.4.4 H5N6 HPAI viruses for assessing their evolutionary process and dissemination pathways.

Project description:Since 2014, highly pathogenic avian influenza (HPAI) H5N6 viruses have circulated in waterfowls and caused human infections in China, posing significant threats to the poultry industry and the public health. However, the genetics, pathogenicity and innate immune response of H5N6 HPAIVs in geese remain largely unknown. In this study, we analyzed the genetic characteristic of the two H5N6 viruses (GS38 and DK09) isolated from apparently healthy domestic goose and duck in live poultry markets (LPMs) of Southern China in 2016. Phylogenetic analysis showed that the HA genes of the two H5N6 viruses belonged to clade 2.3.4.4 and were clustered into the MIX-like group. The MIX-like group viruses have circulated in regions such as China, Japan, Korea, and Vietnam. The NA genes of the two H5N6 viruses were classified into the Eurasian sublineage. The internal genes including PB2, PB1, PA, NP, M, and NS of the two H5N6 viruses derived from the MIX-like. Therefore, our results suggested that the two H5N6 viruses were reassortants of the H5N1 and H6N6 viruses and likely derived from the same ancestor. Additionally, we evaluated the pathogenicity and transmission of the two H5N6 viruses in domestic geese. Results showed that both the two viruses caused serious clinical symptoms in all inoculated geese and led to high mortality in these birds. Both the two viruses were transmitted efficiently to contact geese and caused lethal infection in these birds. Furthermore, we found that mRNA of pattern recognition receptors (PRRs), interferons (IFNs), and stimulated genes (ISGs) exhibited different levels of activation in the lungs and spleens of the two H5N6 viruses-inoculated geese though did not protect these birds from H5N6 HPAIVs infection. Our results suggested that the clade 2.3.4.4 waterfowl-origin H5N6 HPAIVs isolated from LPMs of Southern China could cause high mortality in geese and innate immune-related genes were involved in the geese innate immune response to H5N6 HPAIVs infection. Therefore, we should pay more attention to the evolution, pathogenic variations of these viruses and enhance virological surveillance of clade 2.3.4.4 H5N6 HPAIVs in waterfowls in China.

Dataset Information

Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses.

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