Dataset Information

Immune-Related Gene Expression in Ducks Infected With Waterfowl-Origin H5N6 Highly Pathogenic Avian Influenza Viruses.

ABSTRACT: Clade 2.3.4.4 H5 avian influenza viruses (AIVs) are widely prevalent and of significant concern to the poultry industry and public health in China. Nowadays, the clade 2.3.4.4 H5N6 virus has become a dominant AIV subtype among domestic ducks in southern China. We found that waterfowl-origin clade 2.3.4.4 H5N6 viruses (A/goose/Guangdong/16568/2016, GS16568 and A/duck/Guangdong/16873/2016, DK16873) isolated from southern China in 2016 could replicate in multiple organs of inoculated ducks. DK16873 virus caused mild infections and killed 2/5 of inoculated ducks, and GS16568 virus did not kill inoculated ducks. In addition, the two viruses could be transmitted via direct contact between ducks. DK16873 and GS16568 viruses killed 2/5 and 1/5 of contact ducks, respectively. Furthermore, ducks inoculated with the two H5N6 viruses exhibited different expressions of immune-related genes in their lungs. The expression of RIG-I, TLR3 and IL6 was significantly upregulated at 12 h post-inoculation (HPI) and most of the tested immune-related genes were significantly upregulated at 3 days post-inoculation (DPI). Notably, the expression of RIG-I and IL-6 in response to DK16873 virus was significantly higher than for GS16568 virus at 12 HPI and 3 DPI. Our research have provided helpful information about the pathogenicity, transmission and immune-related genes expression in ducks infected with new H5N6 AIVs.

SUBMITTER: Wu S

PROVIDER: S-EPMC6687855 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Immune-Related Gene Expression in Ducks Infected With Waterfowl-Origin H5N6 Highly Pathogenic Avian Influenza Viruses.

Wu Siyu S Zhang Junsheng J Huang Jianni J Li Weiqiang W Liu Zhiting Z He Zhuoliang Z Chen Zuxian Z He Wanting W Zhao Bingbing B Qin Zhifeng Z Jiao Peirong P Liao Ming M

Frontiers in microbiology 20190802

Clade 2.3.4.4 H5 avian influenza viruses (AIVs) are widely prevalent and of significant concern to the poultry industry and public health in China. Nowadays, the clade 2.3.4.4 H5N6 virus has become a dominant AIV subtype among domestic ducks in southern China. We found that waterfowl-origin clade 2.3.4.4 H5N6 viruses (A/goose/Guangdong/16568/2016, GS16568 and A/duck/Guangdong/16873/2016, DK16873) isolated from southern China in 2016 could replicate in multiple organs of inoculated ducks. DK16873 ...[more]

PMID: 31428075

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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.

Project description:Clade 2.3.4.4 H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused outbreaks in poultry in the world. Some of these viruses acquired internal genes from other subtype avian influenza viruses (AIVs) such as H9 and H6 for the generation of novel reassortant viruses and continually circulated in poultry. Here, we applied a duck-origin virus DK87 and a chicken-origin virus CK66 to assess the biological characteristics of novel reassortant H5N6 HPAIVs and its pathogenesis in ducks. A genetic analysis indicated that the HA genes of the two H5N6 HPAIVs were closely related to the H5 viruses of clade 2.3.4.4 circulating in Eastern Asia and classified into H5 AIV/Eastern Asia (EA)-like lineage. Their NA genes fell into Eurasian lineage had close relationship with those of H5N6 viruses circulating in China, Laos, Vietnam, Japan, and Korea. All internal genes of DK87 were aggregated closely with H5 AIV/EA-like viruses. The internal genes (PB1, PA, NP, M, and NS) of CK66 were derived from H9N2 AIV/SH98-like viruses and the PB2 were derived from H5 AIV/EA-like viruses. These results indicate that clade 2.3.4.4 H5N6 AIVs have continually evolved and recombined with the H9N2 viruses circulating in Southern China. Pathogenicity test showed that the two viruses displayed a broader tissue distribution in ducks and caused no clinical signs. These results indicated that ducks were permissive for the replication of the chicken-origin reassortant virus CK66 without prior adaptation, but the duck-origin virus DK87-inoculated ducks showed significantly higher viral titers in some organs than the CK66-inoculated ducks at 5 day post-inoculated (DPI). The recovery of viruses from oropharyngea and cloacal swabs of contacted ducks indicated that they transmitted in native ducks by direct contact. Quantitative reverse transcription PCR (qRT-PCR) results revealed that the immune-relative genes (PRRs, IFNs, Mx-1, IL-6, and IL-8) in the lungs of inoculated ducks were expressed regardless of virus origin, but the expression of these genes was significantly higher in response to infection with the DK87 virus compared to the CK66 virus at 3 DPI. Overall, we should provide further insights into how clade 2.3.4.4 H5N6 AIVs undergo genetic and pathogenic variations to prevent outbreaks of this disease.

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.

Dataset Information

Immune-Related Gene Expression in Ducks Infected With Waterfowl-Origin H5N6 Highly Pathogenic Avian Influenza Viruses.

Publications

Immune-Related Gene Expression in Ducks Infected With Waterfowl-Origin H5N6 Highly Pathogenic Avian Influenza Viruses.

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