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Background Hemagglutinin is a major surface protein in influenza A virus (IAV), and HA2 is relative conserved among different IAVs. It will be meaningful to identify broad-spectrum epitopes based on the HA2 protein. Results Overlapping peptides of the HA2 protein of the H5N1 IAV A/Mallard/Huadong/S/2005 were synthesized and loaded on modified silica gel film to form a microarray, and antisera against different subtypes of IAVs were used to screen universal epitopes. The selected epitope was further confirmed by western blotting using anti-peptide immune serum and viruses rescued with amino acid substitution. The results showed that 485-FYHKCDNECME-495 of the H5 14th peptide in HA2 had broad-spectrum binding activity with antisera against H1, H3, H4, H5, H6, H7, H8, H9, and H10 subtype IAV. Substitution of amino acids (K or D) in rescued viruses resulted in decreased serum binding, indicating that they were critical residues for serum binding activity. In Immune Epitope Database, some epitopes containing 14–4 peptide were confirmed as MHC-II-restricted CD4 T cell epitope and had effects on releasing IL-2 or IFN. Conclusion The identified epitope should be a novel universal target for detection and vaccine design and its ability to generate immune protection needs further exploration.
Qiuxia Wang; Zhihao Sun; Jingzhi Li; Tao Qin; Hongwei Ma; Sujuan Chen; Daxin Peng; Xiufan Liu. Identification of a universal antigen epitope of influenza A virus using peptide microarray. BMC Veterinary Research 2021, 17, 1 -12.
AMA StyleQiuxia Wang, Zhihao Sun, Jingzhi Li, Tao Qin, Hongwei Ma, Sujuan Chen, Daxin Peng, Xiufan Liu. Identification of a universal antigen epitope of influenza A virus using peptide microarray. BMC Veterinary Research. 2021; 17 (1):1-12.
Chicago/Turabian StyleQiuxia Wang; Zhihao Sun; Jingzhi Li; Tao Qin; Hongwei Ma; Sujuan Chen; Daxin Peng; Xiufan Liu. 2021. "Identification of a universal antigen epitope of influenza A virus using peptide microarray." BMC Veterinary Research 17, no. 1: 1-12.
H5N8 subtype highly pathogenic avian influenza viruses (HPAIVs) pose a huge threat to poultry industry and general public health. Our previous study demonstrated that synergistic effect of 283M and 526R in PB2 gene was a critical factor for viral high pathogenicity in mammals. However, the potential pathogenic mechanism of the mutant virus is still unclear. Here, RNA-seq method was used to analyze the global host response of murine lungs after infecting with parental r-JY virus and JY-PB2-I283M-K526R mutant virus. We found that both amounts and the expression levels of host differentially expressed genes (DEGs) were higher in mutant virus-infected mice compared with the group of parental virus. Furthermore, the DEGs mainly related with innate immune response by GO and KEGG analysis. Especially, PB2-I283M-K526R mutation strongly induced a sharp expression of cytokine storm-related genes, including MX1, CXCL10, and IFN-γ, performed by qRT-PCR. We also found that PB2-I283M-K526R mutation accelerated the level of cell apoptosis by heat map analysis of apoptosis-related DEGs in lungs and apoptosis assay in vitro. Taken together, our data demonstrated that PB2-I283M-K526R of H5N8 subtype HPAIV exacerbated the innate immune response and the level of cell apoptosis, which might be a key pathogenic mechanism for the enhanced pathogenicity of mutants in mammals.
Sujuan Chen; Xiao Wang; Xiang Su; Xinyu Miao; Tao Qin; Daxin Peng; Xiufan Liu. Deep sequencing of the transcriptome from murine lung infected with H5N8 subtype avian influenza virus with combined substitutions I283M and K526R in PB2 gene. Infection, Genetics and Evolution 2020, 87, 104672 .
AMA StyleSujuan Chen, Xiao Wang, Xiang Su, Xinyu Miao, Tao Qin, Daxin Peng, Xiufan Liu. Deep sequencing of the transcriptome from murine lung infected with H5N8 subtype avian influenza virus with combined substitutions I283M and K526R in PB2 gene. Infection, Genetics and Evolution. 2020; 87 ():104672.
Chicago/Turabian StyleSujuan Chen; Xiao Wang; Xiang Su; Xinyu Miao; Tao Qin; Daxin Peng; Xiufan Liu. 2020. "Deep sequencing of the transcriptome from murine lung infected with H5N8 subtype avian influenza virus with combined substitutions I283M and K526R in PB2 gene." Infection, Genetics and Evolution 87, no. : 104672.
Avian influenza virus (AIV) emerged and has continued to re-emerge, continuously posing great threats to animal and human health. The detection of hemagglutination inhibition (HI) or virus neutralization antibodies (NA) is essential for assessing immune protection against AIV. However, the HI/NA-independent immune protection is constantly observed in vaccines' development against H7N9 subtype AIV and other subtypes in chickens and mammals, necessitating the analysis of the cellular immune response. Here, we established a multi-parameter flow cytometry to examine the innate and adaptive cellular immune responses in chickens after intranasal infection with low pathogenicity H7N9 AIV. This assay allowed us to comprehensively define chicken macrophages, dendritic cells, and their MHC-II expression, NK cells, γδ T cells, B cells, and distinct T cell subsets in steady state and during infection. We found that NK cells and KUL01+ cells significantly increased after H7N9 infection, especially in the lung, and the KUL01+ cells upregulated MHC-II and CD11c expression. Additionally, the percentages and numbers of γδ T cells and CD8 T cells significantly increased and exhibited an activated phenotype with significant upregulation of CD25 expression in the lung but not in the spleen and blood. Furthermore, B cells showed increased in the lung but decreased in the blood and spleen in terms of the percentages or/and numbers, suggesting these cells may be recruited from the periphery after H7N9 infection. Our study firstly disclosed that H7N9 infection induced local and systemic cellular immune responses in chickens, the natural host of AIV, and that the flow cytometric assay developed in this study is useful for analyzing the cellular immune responses to AIVs and other avian infectious diseases and defining the correlates of immune protection.
Xiaoli Hao; Shuai Li; Lina Chen; Maoli Dong; Jiongjiong Wang; Jiao Hu; Min Gu; Xiaoquan Wang; Shunlin Hu; Daxin Peng; Xiufan Liu; Shaobin Shang. Establishing a Multicolor Flow Cytometry to Characterize Cellular Immune Response in Chickens Following H7N9 Avian Influenza Virus Infection. Viruses 2020, 12, 1396 .
AMA StyleXiaoli Hao, Shuai Li, Lina Chen, Maoli Dong, Jiongjiong Wang, Jiao Hu, Min Gu, Xiaoquan Wang, Shunlin Hu, Daxin Peng, Xiufan Liu, Shaobin Shang. Establishing a Multicolor Flow Cytometry to Characterize Cellular Immune Response in Chickens Following H7N9 Avian Influenza Virus Infection. Viruses. 2020; 12 (12):1396.
Chicago/Turabian StyleXiaoli Hao; Shuai Li; Lina Chen; Maoli Dong; Jiongjiong Wang; Jiao Hu; Min Gu; Xiaoquan Wang; Shunlin Hu; Daxin Peng; Xiufan Liu; Shaobin Shang. 2020. "Establishing a Multicolor Flow Cytometry to Characterize Cellular Immune Response in Chickens Following H7N9 Avian Influenza Virus Infection." Viruses 12, no. 12: 1396.
NS gene is generally considered to be related to the virulence of highly pathogenic avian influenza virus (AIV). In recent years, the strains with five amino acids added to the 80-84 positions of the NS1 protein have become prevalent in H5N1 subtype AIVs isolated from mammals. However, the pathogenicity and mechanism of this pattern in mammals remain unclear. In this study, H5N1 subtype AIVs without 80-84 amino acids of the NS1 protein (rNSΔ5aa ) and a mutant virus (rNS5aa-R ) with no deletion of 80-84 amino acids of the NS1 protein were used to determine the pathogenicity in mice. Our results showed that rNS5aa-R possessed an enhanced pathogenicity compared with rNSΔ5aa in vivo and in vitro, which was accompanied by high expression of IL-6, MX1 and CXCL10 in murine lungs. Furthermore, we found that rNS5aa-R increased the infection ability to dendritic cells (DCs). Besides, rNS5aa-R enhanced the expression of phenotypic markers (CD80, CD86, CD40 and MHCII), activation marker CD69, inflammatory cytokines (IL-6, TNF-α and IL-10) and antagonized interferon (IFN-α) of DCs, in comparison to rNSΔ5aa . Moreover, rNS5aa-R induced DCs to quickly migrate into nearby cervical lymph nodes by highly upregulating CCR7, and CD86 showed a high expression on the migrated DCs. We also found that rNS5aa-R -infected DCs significantly promoted the allogeneic CD4+ T-cell proliferation. These findings suggested that rNS5aa-R strongly induced the innate immune response compared with the rNSΔ5aa , which is conducive to activate a wide immune response, resulting in a strong cytokine storm and causing an enhanced pathogenicity of H5N1 subtype AIVs in mammals.
Sujuan Chen; Xinyu Miao; Dandan Huangfu; Xinyi Zhao; Minxia Zhang; Tao Qin; Daxin Peng; Xiufan Liu. H5N1 avian influenza virus without 80–84 amino acid deletion at the NS1 protein hijacks the innate immune system of dendritic cells for an enhanced mammalian pathogenicity. Transboundary and Emerging Diseases 2020, 1 .
AMA StyleSujuan Chen, Xinyu Miao, Dandan Huangfu, Xinyi Zhao, Minxia Zhang, Tao Qin, Daxin Peng, Xiufan Liu. H5N1 avian influenza virus without 80–84 amino acid deletion at the NS1 protein hijacks the innate immune system of dendritic cells for an enhanced mammalian pathogenicity. Transboundary and Emerging Diseases. 2020; ():1.
Chicago/Turabian StyleSujuan Chen; Xinyu Miao; Dandan Huangfu; Xinyi Zhao; Minxia Zhang; Tao Qin; Daxin Peng; Xiufan Liu. 2020. "H5N1 avian influenza virus without 80–84 amino acid deletion at the NS1 protein hijacks the innate immune system of dendritic cells for an enhanced mammalian pathogenicity." Transboundary and Emerging Diseases , no. : 1.
Background: Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens. Antigenic mutation of infectious laryngotracheitis virus (ILTV) may result in a vaccination failure in the poultry industry and thus a protective vaccine against predominant ILTV strains is highly desirable. Methods: The full-length glycoprotein B (gB) gene of ILTV with the two mutated synonymous sites of fowlpox virus (FPV) transcription termination signal sequence was cloned into the insertion vector p12LS, which was co-transfected with wild-type (wt) FPV into chicken embryo fibroblast (CEF) to develop a recombinant fowlpox virus-gB (rFPV-gB) candidate vaccine strain. Furthermore, its biological and immunological characteristics were evaluated. Results: The results indicated that gB gene was expressed correctly in the rFPV by indirect immunofluorescent assay and Western blot, and the rFPV-gB provided a 100% protection in immunized chickens against the challenge of predominant ILTV strains that were screened by pathogenicity assay when compared with the commercialized rFPV vaccine, which only provided 83.3%. Conclusion: rFPV-gB can be used as a potential vaccine against predominant ILTV strains.
Sujuan Chen; Nuo Xu; Lei Ta; Shi Li; Xiang Su; Jing Xue; Yinping Du; Tao Qin; Daxin Peng. Recombinant Fowlpox Virus Expressing gB Gene from Predominantly Epidemic Infectious Larygnotracheitis Virus Strain Demonstrates Better Immune Protection in SPF Chickens. Vaccines 2020, 8, 623 .
AMA StyleSujuan Chen, Nuo Xu, Lei Ta, Shi Li, Xiang Su, Jing Xue, Yinping Du, Tao Qin, Daxin Peng. Recombinant Fowlpox Virus Expressing gB Gene from Predominantly Epidemic Infectious Larygnotracheitis Virus Strain Demonstrates Better Immune Protection in SPF Chickens. Vaccines. 2020; 8 (4):623.
Chicago/Turabian StyleSujuan Chen; Nuo Xu; Lei Ta; Shi Li; Xiang Su; Jing Xue; Yinping Du; Tao Qin; Daxin Peng. 2020. "Recombinant Fowlpox Virus Expressing gB Gene from Predominantly Epidemic Infectious Larygnotracheitis Virus Strain Demonstrates Better Immune Protection in SPF Chickens." Vaccines 8, no. 4: 623.
Background Hemagglutinin is a major surface protein in influenza A virus (IAV), and HA2 is relative conserved among different IAVs. However, identification of broad-spectrum epitopes remain less. Results Overlapping peptides of the HA2 protein of the H5N1 IAV A/Mallard/Huadong/S/2005 were synthesized and loaded on modified silica gel film to form a microarray, and antisera against different subtypes of IAVs were used to screen universal epitopes. The selected epitope was further confirmed by western blotting using anti-peptide immune serum and viruses rescued with amino acid substitution. The results showed that 485-FYHKCDNECME-495 of the 14th peptide in HA2 had broad-spectrum binding activity with antisera against H1, H3, H4, H5, H6, H7, H8, H9, and H10 subtype IAV. Substitution of amino acids (K or D) in rescued viruses resulted in decreased serum binding, indicating that they were critical residues for serum binding activity. In Immune Epitope Database, some epitopes containing 14 − 4 peptide were confirmed as MHC-II-restricted CD4 T cell epitope and had effects on releasing IL-2 or IFN. Conclusion The identified epitope should be a novel universal target for diagnostics and its ability to generate immune protection needs further exploration.
Qiuxia Wang; Zhihao Sun; Jingzhi Li; Tao Qin; Hongwei Ma; Sujuan Chen; Daxin Peng; Xiufan Liu. Identification of a Universal Antigen Epitope of Influenza A Virus using Peptide Microarray. 2020, 1 .
AMA StyleQiuxia Wang, Zhihao Sun, Jingzhi Li, Tao Qin, Hongwei Ma, Sujuan Chen, Daxin Peng, Xiufan Liu. Identification of a Universal Antigen Epitope of Influenza A Virus using Peptide Microarray. . 2020; ():1.
Chicago/Turabian StyleQiuxia Wang; Zhihao Sun; Jingzhi Li; Tao Qin; Hongwei Ma; Sujuan Chen; Daxin Peng; Xiufan Liu. 2020. "Identification of a Universal Antigen Epitope of Influenza A Virus using Peptide Microarray." , no. : 1.
Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)‐based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS‐IONzyme increases antigen adhesion to nasal mucosa by 30‐fold compared to H1N1 WIV alone. Next, CS‐IONzyme facilitates H1N1 WIV to enhance CCL20‐driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll‐like receptor(TLR) 2/4‐dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)‐like activity by CS modification catalyzes a reactive oxygen species (ROS)‐dependent DC maturation, which further enhances the migration of H1N1 WIV‐loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS‐IONzyme‐based nasal vaccine triggers an 8.9‐fold increase of IgA‐mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection.
Tao Qin; Shang Ma; Xinyu Miao; Yan Tang; Dandan Huangfu; Jinyuan Wang; Jing Jiang; Nuo Xu; Yuncong Yin; Sujuan Chen; Xiufan Liu; Yinyan Yin; Daxin Peng; Lizeng Gao. Mucosal Vaccination for Influenza Protection Enhanced by Catalytic Immune‐Adjuvant. Advanced Science 2020, 7, 1 .
AMA StyleTao Qin, Shang Ma, Xinyu Miao, Yan Tang, Dandan Huangfu, Jinyuan Wang, Jing Jiang, Nuo Xu, Yuncong Yin, Sujuan Chen, Xiufan Liu, Yinyan Yin, Daxin Peng, Lizeng Gao. Mucosal Vaccination for Influenza Protection Enhanced by Catalytic Immune‐Adjuvant. Advanced Science. 2020; 7 (18):1.
Chicago/Turabian StyleTao Qin; Shang Ma; Xinyu Miao; Yan Tang; Dandan Huangfu; Jinyuan Wang; Jing Jiang; Nuo Xu; Yuncong Yin; Sujuan Chen; Xiufan Liu; Yinyan Yin; Daxin Peng; Lizeng Gao. 2020. "Mucosal Vaccination for Influenza Protection Enhanced by Catalytic Immune‐Adjuvant." Advanced Science 7, no. 18: 1.
In recent years in China, clade 2.3.4.4 H5N6 plus clade 2.3.2.1 H5N1 subtype highly pathogenic avian influenza (HPAI) viruses have gradually become endemic in poultry, and their co‐circulation could inevitably facilitate the gene reassortment between each other. During our routine surveillance in live poultry markets (LPMs) in Eastern China in 2017‐2018, a novel reassortant H5N6 strain with the HA gene derived from clade 2.3.2.1 was isolated from the cloacal swabs of apparently healthy ducks. Phylogenetic tracing analysis indicated that another two clade 2.3.2.1 H5N1 strains with divergent lineages of PB1 gene and one clade 2.3.4.4 H5N6 isolate of the dominant genotype sharing spatio‐temporal proximity were intimately involved in the generation of this rarely reported clade 2.3.2.1 H5N6 reassortant. Distinct with the other three HPAI H5 viruses showing moderate virulence in mice, the H5N1 strain of the homologous internal‐gene constellation against the clade 2.3.2.1 H5N6 reassortant was highly pathogenic which might probably attribute to the H3 subtype‐derived PB1 gene. However, as compared to the clade 2.3.4.4 H5N6 ancestor, the clade 2.3.2.1 H5N6 reassortant displayed a broader tissue distribution and higher viral titers in mice, which could likely facilitate the viral maintenance and spread in nature. Therefore, our results highlight that continuous epidemiological survey of H5 subtype HPAI viruses in LPMs need to be strengthened to prevent the potential poultry or even public health threat of the novel reassortants from endemic viruses.
Zhichuang Ge; Min Gu; Tianyu Cai; Kaituo Liu; Ruyi Gao; Dong Liu; Wenqiang Sun; Xiuli Li; Lei Shi; Jiao Liu; Xiaoquan Wang; Jiao Hu; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. Phylogenetic tracing and biological characterization of a novel clade 2.3.2.1 reassortant of H5N6 subtype avian influenza virus in China. Transboundary and Emerging Diseases 2020, 68, 730 -741.
AMA StyleZhichuang Ge, Min Gu, Tianyu Cai, Kaituo Liu, Ruyi Gao, Dong Liu, Wenqiang Sun, Xiuli Li, Lei Shi, Jiao Liu, Xiaoquan Wang, Jiao Hu, Xiaowen Liu, Shunlin Hu, Sujuan Chen, Daxin Peng, Xinan Jiao, Xiufan Liu. Phylogenetic tracing and biological characterization of a novel clade 2.3.2.1 reassortant of H5N6 subtype avian influenza virus in China. Transboundary and Emerging Diseases. 2020; 68 (2):730-741.
Chicago/Turabian StyleZhichuang Ge; Min Gu; Tianyu Cai; Kaituo Liu; Ruyi Gao; Dong Liu; Wenqiang Sun; Xiuli Li; Lei Shi; Jiao Liu; Xiaoquan Wang; Jiao Hu; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. 2020. "Phylogenetic tracing and biological characterization of a novel clade 2.3.2.1 reassortant of H5N6 subtype avian influenza virus in China." Transboundary and Emerging Diseases 68, no. 2: 730-741.
Background Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood. Methods In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection. Results The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1. Conclusion Collectively, our findings suggest that IAV infection induces SOCS1 expression to promote JAK1 degradation, which in turn inhibits host innate immune responses.
Yinping Du; Fan Yang; Qiuxia Wang; Nuo Xu; Yizhang Xie; Sujuan Chen; Tao Qin; Daxin Peng. Influenza a virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1. Virology Journal 2020, 17, 1 -10.
AMA StyleYinping Du, Fan Yang, Qiuxia Wang, Nuo Xu, Yizhang Xie, Sujuan Chen, Tao Qin, Daxin Peng. Influenza a virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1. Virology Journal. 2020; 17 (1):1-10.
Chicago/Turabian StyleYinping Du; Fan Yang; Qiuxia Wang; Nuo Xu; Yizhang Xie; Sujuan Chen; Tao Qin; Daxin Peng. 2020. "Influenza a virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1." Virology Journal 17, no. 1: 1-10.
BACKGROUND: Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood.METHODS: In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection.RESULTS: The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1. CONCLUSION: Collectively, our findings suggest that IAV infection induces SOCS1 expression to promote JAK1 degradation, which in turn inhibits host innate immune responses.
Yinping Du; Fan Yang; Qiuxia Wang; Nuo Xu; Yizhang Xie; Sujuan Chen; Tao Qin; Da-Xin Peng. Influenza A virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1. 2020, 1 .
AMA StyleYinping Du, Fan Yang, Qiuxia Wang, Nuo Xu, Yizhang Xie, Sujuan Chen, Tao Qin, Da-Xin Peng. Influenza A virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1. . 2020; ():1.
Chicago/Turabian StyleYinping Du; Fan Yang; Qiuxia Wang; Nuo Xu; Yizhang Xie; Sujuan Chen; Tao Qin; Da-Xin Peng. 2020. "Influenza A virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1." , no. : 1.
The Influenza A virus (IAV) PB2 subunit modulates viral polymerase activity, replication kinetics, and pathogenicity. Here we identified novel PB2 substitutions at position 283 of H5 subtype IAV and evaluated their biological characteristics and virulence. The substitution PB2‐M283L enhanced the growth capacity and polymerase activity in human and mammalian cells in comparison to the rWT virus. The substitution PB2‐M283L displayed high virulence, resulting in a greater virus load in different tissues, more severe histopathological lesions, and proinflammatory cytokines burst in mice. The substitution PB2‐M283I had an opposite phenotype. Our data extend the important role of PB2 substitutions in the adaptation of H5 subtype IAVs to mammalian hosts.
Sujuan Chen; Yizhang Xie; Xiang Su; Jing Xue; Xiao Wang; Yinping Du; Tao Qin; Daxin Peng; Xiufan Liu. Substitutions in the PB2 methionine 283 residue affect H5 subtype avian influenza virus virulence. Transboundary and Emerging Diseases 2020, 67, 2554 -2563.
AMA StyleSujuan Chen, Yizhang Xie, Xiang Su, Jing Xue, Xiao Wang, Yinping Du, Tao Qin, Daxin Peng, Xiufan Liu. Substitutions in the PB2 methionine 283 residue affect H5 subtype avian influenza virus virulence. Transboundary and Emerging Diseases. 2020; 67 (6):2554-2563.
Chicago/Turabian StyleSujuan Chen; Yizhang Xie; Xiang Su; Jing Xue; Xiao Wang; Yinping Du; Tao Qin; Daxin Peng; Xiufan Liu. 2020. "Substitutions in the PB2 methionine 283 residue affect H5 subtype avian influenza virus virulence." Transboundary and Emerging Diseases 67, no. 6: 2554-2563.
Hemagglutinin (HA) glycosylation of avian influenza virus (AIV) effects differently depending on the variation of glycosylation position and numbers. The natural mutation on the glycosylation sites of the AIV HA head occurs frequently. Our previous study shows that deletion of 158 or 169 glycosylation site on the HA head of the H5 subtype AIV strain rS‐144‐/158+/169 + increases the viral virulence in mammals, however, the mechanism remains unknown. In this study, several AIVs with different deletions at HA head glycosylation sites 144, 158 or 169 were tested for their biological characteristics to clarify the possible mechanism. We found that rS‐144‐/158‐/169 + and rS‐144‐/158+/169‐ viruses induced higher levels of inflammatory cytokines than rS‐144‐/158+/169 + did in the infected cells, but the TCID50, EID50 and MDT of the viruses showed no difference. Moreover, we found that rS‐144‐/158‐/169 + and rS‐144‐/158+/169‐ viruses induced higher levels of endoplasmic reticulum (ER) stress in the cells. Inhibition of inositol‐requiring enzyme 1α (IRE1α) phosphorylation reduced the inflammation induced by AIV infection. Furthermore, we found that rS‐144‐/158‐/169 + virus activated the c‐Jun N‐terminal kinase (JNK), X‐box binding protein 1 (XBP1), and nuclear factor‐κB pathways by activating IRE1α phosphorylation under ER stress, whereas the rS‐144‐/158+/169‐ virus activated only the JNK pathway by altering IRE1α phosphorylation. In vivo analysis of Kira6 intervention further confirmed that ER stress played a key role in higher virulence for HA head 158 or 169 site de‐glycosylation AIV. Our findings reveal that deletion of additional HA head glycosylation sites 158 or 169 enhanced the AIV virulence via activating of strong ER stress and inflammation.
Yuncong Yin; Shengqing Yu; Yingjie Sun; Tao Qin; Sujuan Chen; Chan Ding; Daxin Peng; Xiufan Liu. Glycosylation deletion of hemagglutinin head in the H5 subtype avian influenza virus enhances its virulence in mammals by inducing endoplasmic reticulum stress. Transboundary and Emerging Diseases 2020, 67, 1492 -1506.
AMA StyleYuncong Yin, Shengqing Yu, Yingjie Sun, Tao Qin, Sujuan Chen, Chan Ding, Daxin Peng, Xiufan Liu. Glycosylation deletion of hemagglutinin head in the H5 subtype avian influenza virus enhances its virulence in mammals by inducing endoplasmic reticulum stress. Transboundary and Emerging Diseases. 2020; 67 (4):1492-1506.
Chicago/Turabian StyleYuncong Yin; Shengqing Yu; Yingjie Sun; Tao Qin; Sujuan Chen; Chan Ding; Daxin Peng; Xiufan Liu. 2020. "Glycosylation deletion of hemagglutinin head in the H5 subtype avian influenza virus enhances its virulence in mammals by inducing endoplasmic reticulum stress." Transboundary and Emerging Diseases 67, no. 4: 1492-1506.
Zeyuan Wang; ZhuoTian Li; Xiang Su; Yiyi Qiao; Weifeng Fan; Haibin Li; Baolan Shi; Tao Qin; Sujuan Chen; Daxin Peng; Xiufan Liu. Enhanced cross-lineage protection induced by recombinant H9N2 avian influenza virus inactivated vaccine. Vaccine 2019, 37, 1736 -1742.
AMA StyleZeyuan Wang, ZhuoTian Li, Xiang Su, Yiyi Qiao, Weifeng Fan, Haibin Li, Baolan Shi, Tao Qin, Sujuan Chen, Daxin Peng, Xiufan Liu. Enhanced cross-lineage protection induced by recombinant H9N2 avian influenza virus inactivated vaccine. Vaccine. 2019; 37 (13):1736-1742.
Chicago/Turabian StyleZeyuan Wang; ZhuoTian Li; Xiang Su; Yiyi Qiao; Weifeng Fan; Haibin Li; Baolan Shi; Tao Qin; Sujuan Chen; Daxin Peng; Xiufan Liu. 2019. "Enhanced cross-lineage protection induced by recombinant H9N2 avian influenza virus inactivated vaccine." Vaccine 37, no. 13: 1736-1742.
The emergent highly pathogenic avian influenza A (H7N9) (HPAI) virus is a major public concern in China. Therefore, it is crucially important to develop an effective vaccine against this virus. In this study, we constructed a baculovirus vaccine expressing the hemagglutinin (HA) of H7N9 strain A/Chicken/Jiaxing/148/2014 (JX148). The recombinant baculovirus (rBac-JX148HA) generated in this study showed good growth in insect cells and good safety, and it stably expressed the HA protein. We compared the immunogenicity and efficacy of the inactivated whole-virus vaccine JX148 and rBac-JX148HA. One chicken in the JX148-treated group died on day 4 post-challenge, and three chickens had typical clinical symptoms (survival rate, 90%; morbidity, 40%). However, no chickens immunized with rBac-JX148HA showed clinical signs during the 14-day observation period. An analysis of viral shedding and viral replication demonstrated that rBac-JX148HA more efficiently inhibited viral shedding and viral replication than the inactivated whole-virus vaccine. Taken together, these results indicate that the inactivated recombinant baculovirus vaccine induces a high hemagglutination inhibition antibody titer, provides complete protection against challenge with the highly pathogenic H7N9 virus, and effectively inhibits viral shedding. Therefore, the candidate vaccine has potential utility in the prevention and control of H7N9 avian influenza and is also appropriate for veterinary vaccines using cell suspension culture technology.
Jiao Hu; Yanyan Liang; Zenglei Hu; Xiaoquan Wang; Min Gu; Rumeng Li; Chunxi Ma; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. Recombinant baculovirus vaccine expressing hemagglutinin of H7N9 avian influenza virus confers full protection against lethal highly pathogenic H7N9 virus infection in chickens. Archives of Virology 2019, 164, 807 -817.
AMA StyleJiao Hu, Yanyan Liang, Zenglei Hu, Xiaoquan Wang, Min Gu, Rumeng Li, Chunxi Ma, Xiaowen Liu, Shunlin Hu, Sujuan Chen, Daxin Peng, Xinan Jiao, Xiufan Liu. Recombinant baculovirus vaccine expressing hemagglutinin of H7N9 avian influenza virus confers full protection against lethal highly pathogenic H7N9 virus infection in chickens. Archives of Virology. 2019; 164 (3):807-817.
Chicago/Turabian StyleJiao Hu; Yanyan Liang; Zenglei Hu; Xiaoquan Wang; Min Gu; Rumeng Li; Chunxi Ma; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. 2019. "Recombinant baculovirus vaccine expressing hemagglutinin of H7N9 avian influenza virus confers full protection against lethal highly pathogenic H7N9 virus infection in chickens." Archives of Virology 164, no. 3: 807-817.
Tao Qin; Jingjing Zhu; Ruonan Ma; Yuncong Yin; Sujuan Chen; Daxin Peng; Xiufan Liu. Cover Image. Transboundary and Emerging Diseases 2018, 65, 1 .
AMA StyleTao Qin, Jingjing Zhu, Ruonan Ma, Yuncong Yin, Sujuan Chen, Daxin Peng, Xiufan Liu. Cover Image. Transboundary and Emerging Diseases. 2018; 65 (6):1.
Chicago/Turabian StyleTao Qin; Jingjing Zhu; Ruonan Ma; Yuncong Yin; Sujuan Chen; Daxin Peng; Xiufan Liu. 2018. "Cover Image." Transboundary and Emerging Diseases 65, no. 6: 1.
Genetic reassortments between highly pathogenic avian influenza (HPAI) H5 subtype viruses with different neuraminidase (NA) subtypes have increased in prevalence since 2010 in wild birds and poultry from China. The HA gene slightly evolved from clade 2.3.4 to clade 2.3.4.4, raising the question of whether novel clade 2.3.4.4 HA broke the balance with N1 but is matched well with NAx to drive viral epidemics. To clarify the role of compatibility between HA and NA on the prevalence of H5Nx subtypes, we constructed 10 recombinant viruses in which the clade 2.3.4 or clade 2.3.4.4 HA genes were matched with different NA (N1, N2 and N8) genes and evaluated viral characteristics and pathogenicity. Combinations between clade 2.3.4 HA and N1 or between clade 2.3.4.4 HA and NAx, but not between clade 2.3.4.4 HA and N1, or between clade 2.3.4 HA and NAx, promoted viral growth, NA activity, thermostability, low‐pH stability and pathogenicity in chicken and mice. These findings suggest that both clade 2.3.4 HA/N1 and clade 2.3.4.4 HA/NAx displayed a better match, which could promote the increased prevalence of clade 2.3.4 H5N1 AIV (prior to 2010) and clade 2.3.4.4 H5Nx AIV (since 2010) in China, respectively.
Tao Qin; Jingjing Zhu; Ruonan Ma; Yuncong Yin; Sujuan Chen; Daxin Peng; Xiufan Liu. Compatibility between haemagglutinin and neuraminidase drives the recent emergence of novel clade 2.3.4.4 H5Nx avian influenza viruses in China. Transboundary and Emerging Diseases 2018, 65, 1757 -1769.
AMA StyleTao Qin, Jingjing Zhu, Ruonan Ma, Yuncong Yin, Sujuan Chen, Daxin Peng, Xiufan Liu. Compatibility between haemagglutinin and neuraminidase drives the recent emergence of novel clade 2.3.4.4 H5Nx avian influenza viruses in China. Transboundary and Emerging Diseases. 2018; 65 (6):1757-1769.
Chicago/Turabian StyleTao Qin; Jingjing Zhu; Ruonan Ma; Yuncong Yin; Sujuan Chen; Daxin Peng; Xiufan Liu. 2018. "Compatibility between haemagglutinin and neuraminidase drives the recent emergence of novel clade 2.3.4.4 H5Nx avian influenza viruses in China." Transboundary and Emerging Diseases 65, no. 6: 1757-1769.
A stem glycosylation site of hemagglutinin (HA) is important to the stability of the HA trimmer. A previous study shows that the stem 10/11 overlap glycosylation site of the H5 subtype avian influenza virus may influence the cleavage of HA, whereas the exact site and its effect on virulence remain unclear. In this study, site-directed mutagenesis was used to generate single or double mutant rSY-Δ10(10NNAT), rSY-Δ11(10NNSA), and rSY-Δ10/11(10NNAA) of the overlapping glycosylation site (10NNST) on the HA of A/Mallard/Huadong/S/2005(SY). By using Western blot analysis, we show that both rSY-Δ11 and rSY-Δ10/11 mutant viruses had significant delay on HA cleavage and a reduced HA molecular mass compared to the wild-type virus rSY, while the rSY-Δ10 mutant virus exhibited a similar HA molecular mass to that of the wild-type virus rSY. Interestingly, both rSY-Δ11 and rSY-Δ10/11 mutant viruses reverted their glycosylation sites at 11N after passage, indicating that 11N is a true and critical glycosylation site. Compared to the wild-type virus rSY, rSY-Δ11 and rSY-Δ10/11 mutant viruses had decreased growth rates, reduced thermo- and pH-stability, decreased pathogenicity, and limited systemic spread. Therefore, our study suggests that the 11N glycosylation site plays a key role in HA cleavage, structural stability and pathogenicity in H5 subtype avian influenza virus.
Yuncong Yin; Xiaojian Zhang; Yiyi Qiao; Xiao Wang; Yangyang Su; Sujuan Chen; Tao Qin; Daxin Peng; Xiufan Liu. Glycosylation at 11Asn on hemagglutinin of H5N1 influenza virus contributes to its biological characteristics. Veterinary Research 2017, 48, 81 -81.
AMA StyleYuncong Yin, Xiaojian Zhang, Yiyi Qiao, Xiao Wang, Yangyang Su, Sujuan Chen, Tao Qin, Daxin Peng, Xiufan Liu. Glycosylation at 11Asn on hemagglutinin of H5N1 influenza virus contributes to its biological characteristics. Veterinary Research. 2017; 48 (1):81-81.
Chicago/Turabian StyleYuncong Yin; Xiaojian Zhang; Yiyi Qiao; Xiao Wang; Yangyang Su; Sujuan Chen; Tao Qin; Daxin Peng; Xiufan Liu. 2017. "Glycosylation at 11Asn on hemagglutinin of H5N1 influenza virus contributes to its biological characteristics." Veterinary Research 48, no. 1: 81-81.
Highly pathogenic avian influenza (HPAI) H5N8 virus has caused considerable economic losses to poultry industry and poses a great threat to public health. Our previous study revealed two genetically similar HPAI H5N8 viruses displaying completely different virulence in mice. However, the molecular basis for viral pathogenicity to mammals remains unknown. Herein, we generated a series of reassortants between the two viruses and evaluated their virulence in mice. We demonstrated that 283M in PB2 is a new mammalian virulence marker for H5 viruses and that synergistic effect of amino acid residues 283M and 526R in PB2 is responsible for high virulence of the HPAI H5N8 virus. Analysis of available PB2 sequences showed that PB2 283M is highly conserved among influenza A viruses, while PB2 526R presents in most of human H3N2 and H5N1 isolates. Further study confirmed that the residues 283M and 526R had similar impacts on an HPAI H5N1 virus, suggesting that influenza viruses with both residues may replicate well in mammalian hosts. Together, these results present new insights for synergistic effect of 283M and 526R in PB2 of H5 HPAI virus on virulence to mammalian host, furthering our understanding of the pathogenesis of influenza A virus.
Xiao Wang; Sujuan Chen; Dandan Wang; Xixin Zha; Siwen Zheng; Tao Qin; Wenjun Ma; Daxin Peng; Xiufan Liu. Synergistic effect of PB2 283M and 526R contributes to enhanced virulence of H5N8 influenza viruses in mice. Veterinary Research 2017, 48, 67 -67.
AMA StyleXiao Wang, Sujuan Chen, Dandan Wang, Xixin Zha, Siwen Zheng, Tao Qin, Wenjun Ma, Daxin Peng, Xiufan Liu. Synergistic effect of PB2 283M and 526R contributes to enhanced virulence of H5N8 influenza viruses in mice. Veterinary Research. 2017; 48 (1):67-67.
Chicago/Turabian StyleXiao Wang; Sujuan Chen; Dandan Wang; Xixin Zha; Siwen Zheng; Tao Qin; Wenjun Ma; Daxin Peng; Xiufan Liu. 2017. "Synergistic effect of PB2 283M and 526R contributes to enhanced virulence of H5N8 influenza viruses in mice." Veterinary Research 48, no. 1: 67-67.
Nine influenza virus neuraminidase (NA) subtypes have been identified in poultry and wild birds. Few methods are available for rapid and simple NA subtyping. Here we developed a multiplex probe combination-based one-step real-time reverse transcriptase PCR (rRT-PCR) to detect nine avian influenza virus NA subtypes. Nine primer-probe pairs were assigned to three groups based on the different fluorescent dyes of the probes (FAM, HEX, or Texas Red). Each probe detected only one NA subtype, without cross reactivity. The detection limit was less than 100 EID50 or 100 copies of cDNA per reaction. Data obtained using this method with allantoic fluid samples isolated from live bird markets and H9N2-infected chickens correlated well with data obtained using virus isolation and sequencing, but was more sensitive. This new method provides a specific and sensitive alternative to conventional NA-subtyping methods.
Zhihao Sun; Tao Qin; Feifei Meng; Sujuan Chen; Daxin Peng; Xiufan Liu. Development of a multiplex probe combination-based one-step real-time reverse transcription-PCR for NA subtype typing of avian influenza virus. Scientific Reports 2017, 7, 13455 .
AMA StyleZhihao Sun, Tao Qin, Feifei Meng, Sujuan Chen, Daxin Peng, Xiufan Liu. Development of a multiplex probe combination-based one-step real-time reverse transcription-PCR for NA subtype typing of avian influenza virus. Scientific Reports. 2017; 7 (1):13455.
Chicago/Turabian StyleZhihao Sun; Tao Qin; Feifei Meng; Sujuan Chen; Daxin Peng; Xiufan Liu. 2017. "Development of a multiplex probe combination-based one-step real-time reverse transcription-PCR for NA subtype typing of avian influenza virus." Scientific Reports 7, no. 1: 13455.
H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses towards these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14 and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.
Sujuan Chen; Yinbiao Zhu; Da Yang; Yang Yang; Shaohua Shi; Tao Qin; Daxin Peng; Xiufan Liu. Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses. Frontiers in Microbiology 2017, 8, 1086 -1086.
AMA StyleSujuan Chen, Yinbiao Zhu, Da Yang, Yang Yang, Shaohua Shi, Tao Qin, Daxin Peng, Xiufan Liu. Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses. Frontiers in Microbiology. 2017; 8 ():1086-1086.
Chicago/Turabian StyleSujuan Chen; Yinbiao Zhu; Da Yang; Yang Yang; Shaohua Shi; Tao Qin; Daxin Peng; Xiufan Liu. 2017. "Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses." Frontiers in Microbiology 8, no. : 1086-1086.