Publications by authors named "Xiufan Liu"

309 Publications

Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020.

Emerg Infect Dis 2022 Aug;28(8):1664-1668

We investigated genetic and biologic characteristics of 2 Eurasian avian-like H1N1 swine influenza viruses from pigs in China that belong to the predominant G4 genotype. One swine isolate exhibited strikingly great homology to contemporaneous human Eurasian avian-like H1N1 isolates, preferential binding to the human-type receptor, and vigorous replication in mice without adaptation.
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http://dx.doi.org/10.3201/eid2808.212530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328894PMC
August 2022

PA-X protein assists H9N2 subtype avian influenza virus in escaping immune response of mucosal dendritic cells.

Transbound Emerg Dis 2022 Jul 20. Epub 2022 Jul 20.

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.

H9N2 subtype low pathogenicity avian influenza virus (AIV) poses a potential zoonotic risk. PA-X, a novel protein generated by PA gene ribosomal frameshift, is considered to be the virulence factor of H9N2 subtype AIVs. Our study found that rTX possessing PA-X protein enhanced the mammalian pathogenicity of H9N2 subtype AIVs compared with PA-X-deficient virus (rTX-FS). Furthermore, PA-X protein inhibited H9N2 subtype AIVs to infect dendritic cells (DCs), but not nonimmune cells (MDCK cells). Meanwhile, PA-X protein suppressed the phenotypic expression (CD80, CD86, CD40 and MHCII), early activation marker (CD69) and pro-inflammatory cytokines (IL-6 and TNF-α), whereas increased anti-inflammatory cytokine (IL-10) in DCs. After intranasally viral infection in mice, we found that PA-X protein of H9N2 subtype AIVs reduced CD11b and CD103 subtype mucosal DCs recruitment to the nasal submucosa by inhibiting CCL20 expression. Moreover, PA-X protein abolished the migratory ability of CD11b and CD103 DCs into draining cervical lymph nodes by down-regulating CCR7 expression. The rTX-infected DCs significantly impaired the allogeneic CD4 T cell proliferation, suggesting PA-X protein suppressed the immune functions of DCs for hindering the downstream immune activation. These findings indicated that PA-X protein assisted H9N2 subtype AIVs in escaping immune response of mucosal DCs for enhancing the pathogenicity.
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http://dx.doi.org/10.1111/tbed.14665DOI Listing
July 2022

Foreign gene expression attenuates a virulent Newcastle disease virus in chickens.

Virus Genes 2022 Jun 25. Epub 2022 Jun 25.

Key Laboratory of Animal Infectious Diseases, School of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Newcastle disease virus (NDV) is an important pathogen for poultry and is used as a vector for developing novel poultry vaccines. Previous studies showed that foreign gene insertion in NDV vector decreases virulence determined by in vitro assays; however, the impact of foreign gene expression on the pathogenicity of NDV in susceptible chickens is not fully investigated. In this study, a recombinant NDV based on a velogenic strain carrying the orange fluorescent protein (OFP) gene between the phosphoprotein (P) and matrix (M) genes was generated using reverse genetics. Biological characteristics, including virus replication, virulence, and OFP expression, and the pathogenicity in chickens were evaluated. The recombinant NDV showed comparable replication capacity in eggs and cells as the parental virus, whereas OFP insertion resulted in a mild impairment of virulence, evidenced by longer mean death time in embryos. High OFP expression was detected in the cells inoculated with the recombinant NDV. In addition, the recombinant NDV induced delayed onset of disease, lower severity of clinical signs, and lower mortality in chickens compared to the parental virus. Moreover, high titers of the parental virus were detected in the spleen, lung, and intestinal tract, while no recombinant NDV was recovered from these tissues. Our findings suggest that in vitro characteristics related to the insertion of the OFP gene in a virulent NDV do not correlate to alteration of the pathogenicity in chickens. Our results provided new information regarding assessment of the impact of foreign gene expression on the pathogenicity of NDV.
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http://dx.doi.org/10.1007/s11262-022-01922-8DOI Listing
June 2022

Genome-Wide Reassortment Analysis of Influenza A H7N9 Viruses Circulating in China during 2013-2019.

Viruses 2022 06 9;14(6). Epub 2022 Jun 9.

Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Reassortment with the H9N2 virus gave rise to the zoonotic H7N9 avian influenza virus (AIV), which caused more than five outbreak waves in humans, with high mortality. The frequent exchange of genomic segments between H7N9 and H9N2 has been well-documented. However, the reassortment patterns have not been described and are not yet fully understood. Here, we used phylogenetic analyses to investigate the patterns of intersubtype and intrasubtype/intralineage reassortment across the eight viral segments. The H7N9 virus and its progeny frequently exchanged internal genes with the H9N2 virus but rarely with the other AIV subtypes. Before beginning the intrasubtype/intralineage reassortment analyses, five Yangtze River Delta (YRD A-E) and two Pearl River Delta (PRD A-B) clusters were divided according to the HA gene phylogeny. The seven reset segment genes were also nomenclatured consistently. As revealed by the tanglegram results, high intralineage reassortment rates were determined in waves 2-3 and 5. Additionally, the clusters of PB2 c05 and M c02 were the most dominant in wave 5, which could have contributed to the onset of the largest H7N9 outbreak in 2016-2017. Meanwhile, a portion of the YRD-C cluster (HP H7N9) inherited their PB2, PA, and M segments from the co-circulating YRD-E (LP H7N9) cluster during wave 5. Untanglegram results revealed that the reassortment rate between HA and NA was lower than HA with any of the other six segments. A multidimensional scaling plot revealed a robust genetic linkage between the PB2 and PA genes, indicating that they may share a co-evolutionary history. Furthermore, we observed relatively more robust positive selection pressure on HA, NA, M2, and NS1 proteins. Our findings demonstrate that frequent reassortment, particular reassorted patterns, and adaptive mutations shaped the H7N9 viral genetic diversity and evolution. Increased surveillance is required immediately to better understand the current state of the HP H7N9 AIV.
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http://dx.doi.org/10.3390/v14061256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230085PMC
June 2022

Amino Acid Mutations in Hemagglutinin-Neuraminidase Enhance the Virulence and Pathogenicity of the Genotype III Newcastle Disease Vaccine Strain After Intravenous Inoculation.

Front Vet Sci 2022 27;9:890657. Epub 2022 May 27.

Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Newcastle disease virus (NDV), the causative agent that generally causes severe disease in poultry, continues to mutate and has thus evolved into 21 genotypes. We previously isolated a velogenic genotype III NDV JS/7/05/Ch that evolved from the vaccine strain Mukteswar, accompanying by amino acid mutations in Hemagglutinin-Neuraminidase (HN). Here, we sought to investigate the role of the mutant HN protein in NDV virulence. The HN genes of Mukteswar and JS/7/05/Ch were replaced reciprocally via reverse genetics, yielding two recombinant viruses rJS/MHN and rMu/JHN, respectively. rMu/JHN, in which the endogenous HN protein was replaced with the HN protein of JS/7/05/Ch, had a higher intravenous pathogenicity index (IVPI) value in chickens. Moreover, dual aa mutations (A494D and E495K from JS/7/05/Ch-type HN) were introduced into the HN protein of Mukteswar to generate the recombinant virus rMukHN494+495. This virus showed an equivalent IVPI value to that of rJS/7/05/Ch (generated from parental JS/7/05/Ch via reverse genetics). and assays further showed that A494D and E495K in HN induced antigenic changes, a higher replication level and a more intense inflammatory response. Taken together, these findings indicate that aa mutations in HN are crucial for the virulence of the genotype III Newcastle disease (ND) vaccine strain after intravenous inoculation. Our study further highlights that close surveillance is needed to monitor the genetic variation of ND vaccine strains.
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http://dx.doi.org/10.3389/fvets.2022.890657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196742PMC
May 2022

HA gene amino acid mutations contribute to antigenic variation and immune escape of H9N2 influenza virus.

Vet Res 2022 Jun 15;53(1):43. Epub 2022 Jun 15.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China.

Based on differences in the amino acid sequence of the protein haemagglutinin (HA), the H9N2 avian influenza virus (H9N2 virus) has been clustered into multiple lineages, and its rapidly ongoing evolution increases the difficulties faced by prevention and control programs. The HA protein, a major antigenic protein, and the amino acid mutations that alter viral antigenicity in particular have always been of interest. Likewise, it has been well documented that some amino acid mutations in HA alter viral antigenicity in the H9N2 virus, but little has been reported regarding how these antibody escape mutations affect antigenic variation. In this study, we were able to identify 15 HA mutations that were potentially relevant to viral antigenic drift, and we also found that a key amino acid mutation, A180V, at position 180 in HA (the numbering for mature H9 HA), the only site of the receptor binding sites that is not conserved, was directly responsible for viral antigenic variation. Moreover, the recombinant virus with alanine to valine substitution at position 180 in HA in the SH/F/98 backbone (rF/HA virus) showed poor cross-reactivity to immune sera from animals immunized with the SH/F/98 (F/98, A180), SD/SS/94 (A180), JS/Y618/12 (T180), and rF/HA (V180) viruses by microneutralization (MN) assay. The A180V substitution in the parent virus caused a significant decrease in cross-MN titres by enhancing the receptor binding activity, but it did not physically prevent antibody (Ab) binding. The strong receptor binding avidity prevented viral release from cells. Moreover, the A180V substitution promoted H9N2 virus escape from an in vitro pAb-neutralizing reaction, which also slightly affected the cross-protection in vivo. Our results suggest that the A180V mutation with a strong receptor binding avidity contributed to the low reactors in MN/HI assays and slightly affected vaccine efficacy but was not directly responsible for immune escape, which suggested that the A180V mutation might play a key role in the process of the adaptive evolution of H9N2 virus.
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http://dx.doi.org/10.1186/s13567-022-01058-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202205PMC
June 2022

Intranasal Immunization with a Recombinant Avian Paramyxovirus Serotypes 2 Vector-Based Vaccine Induces Protection against H9N2 Avian Influenza in Chicken.

Viruses 2022 04 28;14(5). Epub 2022 Apr 28.

Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou 225000, China.

Commercial inactivated vaccines against H9N2 avian influenza (AI) have been developed in China since 1990s and show excellent immunogenicity with strong HI antibodies. However, currently approved vaccines cannot meet the clinical demand for a live-vectored vaccine. Newcastle disease virus (NDV) vectored vaccines have shown effective protection in chickens against H9N2 virus. However, preexisting NDV antibodies may affect protective efficacy of the vaccine in the field. Here, we explored avian paramyxovirus serotype 2 (APMV-2) as a vector for developing an H9N2 vaccine via intranasal delivery. APMV-2 belongs to the same genus as NDV, distantly related to NDV in the phylogenetic tree, based on the sequences of Fusion (F) and hemagglutinin-neuraminidase (HN) gene, and has low cross-reactivity with anti-NDV antisera. We incorporated hemagglutinin (HA) of H9N2 into the junction of P and M gene in the APMV-2 genome by being flanked with the gene start, gene end, and UTR of each gene of APMV-2-T4 to generate seven recombinant APMV-2 viruses rAPMV-2/HAs, rAPMV-2-NPUTR-HA, rAPMV-2-PUTR-HA, rAPMV-2-FUTR-HA, rAPMV-2-HNUTR-HA, rAPMV-2-LUTR-HA, and rAPMV-2-MUTR-HA, expressing HA. The rAPMV-2/HAs displayed similar pathogenicity compared with the parental APMV-2-T4 virus and expressed HA protein in infected CEF cells. The NP-UTR facilitated the expression and secretion of HA protein in cells infected with rAPMV-2-NPUTR-HA. Animal studies demonstrated that immunization with rAPMV-2-NPUTR-HA elicited effective H9N2-specific antibody (6.14 ± 1.2 log2) responses and conferred complete immune protection to prevent viral shedding in the oropharyngeal and cloacal swabs from chickens challenged with H9N2 virus. This study suggests that our recombinant APMV-2 virus is safe and immunogenic and can be a useful tool in the combat of H9N2 outbreaks in chicken.
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http://dx.doi.org/10.3390/v14050918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144924PMC
April 2022

Emerging of H5N6 Subtype Influenza Virus with 129-Glycosylation Site on Hemagglutinin in Poultry in China Acquires Immune Pressure Adaption.

Microbiol Spectr 2022 Jun 21;10(3):e0253721. Epub 2022 Apr 21.

College of Veterinary Medicine, Yangzhou Universitygrid.268415.c, Yangzhou, Jiangsu, China.

For an investigation into the effects of glycosylation site modification on hemagglutinin (HA) on the biological characteristics of the H5N6 subtype avian influenza virus (AIV), the HA sequences of H5N6 AIVs from Global Initiative on Sharing All Influenza Data (GISAID) and the isolates in China were analyzed for genetic evolution and glycosylation site patterns. Eight recombinant H5N6 AIVs with different glycosylation site patterns were constructed, and their biological characteristics were determined. The results showed that H5N6 AIVs containing a 129-glycosylation site on HA are becoming prevalent strains in China. Acquisition of the 129-glycosylation site on the HA of H5N6 AIVs increased thermostability, decreased pH stability, and attenuated pathogenicity and contact transmission in chickens. Most importantly, H5N6 AIVs escaped the neutralization activity of the Re-8-like serum antibody. Our findings reveal that H5N6 AIVs containing the 129-glycosylation site affect antigenicity and have become prevalent strains in China. H5N6 avian influenza viruses (AIVs) were first reported in 2013 and have spread throughout many countries. In China, compulsory vaccine inoculation has been adopted to control H5 subtype avian influenza. However, the effect of vaccination on the antigenic drift of H5N6 AIVs remains unknown. Here, we found that H5N6 AIVs with the 129-glycosylation site on hemagglutinin were the dominant strains in poultry in China. The neutralization assay of the serum antibody against the H5 subtype vaccine Re-8 showed a significantly lower neutralization activity against H5N6 AIVs with the 129-glycosylation site compared to that against H5N6 AIVs without the 129-glycosylation site, indicating that the 129-glycosylation site may be a crucial molecular marker for immune evasion.
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http://dx.doi.org/10.1128/spectrum.02537-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241720PMC
June 2022

Characterization of two chicken origin highly pathogenic H7N9 viruses isolated in northern China.

Vet Microbiol 2022 May 8;268:109394. Epub 2022 Mar 8.

Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China; Jiangsu Key Laboratory of Zoonoses, Yangzhou University, Yangzhou, China. Electronic address:

Since the national vaccination program was implemented with the H5/H7 bivalent vaccine in poultry in September 2017, the prevalence of H7N9 avian influenza viruses (AIVs) has been controlled effectively in China. However, highly pathogenic H7N9 viruses still exist, causing sporadic outbreaks especially in some regions of northern China. During our routine surveillance in poultry in 2020, we isolated two strains of H7N9 subtype AIV from breeder layer farms in northern China. We found that these two chicken-origin H7N9 isolates were both highly pathogenic (HP) with a four-amino-acid (KRTA) insertion and an I326V mutation (H3 numbering) in the cleavage site of HA to make the motif PEVPKRKRTAR↓GLF. Molecular markers associated with antigenic drift and enhanced pathogenicity in mammals and interspecies transmission were detected in both isolates. Remarkably, both strains gained the F102V and N157D mutations in their HA genes, which have never been reported before. Solid-phase direct binding assay showed that these two isolates both had dual-receptor binding characteristics, while thermal and acid stability assays indicated that they were relatively stable in high-temperature or acidic conditions. In addition, the animal experiments demonstrated that both strains were highly pathogenic to chickens but low pathogenic to mice. These results suggested that the evolution of H7N9 subtype AIV is still continuing, and they pose a potential threat to poultry and public health. Thus, attention should be paid to the importance of continual surveillance of the H7N9 AIVs.
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http://dx.doi.org/10.1016/j.vetmic.2022.109394DOI Listing
May 2022

Characterization of antibody response to an epitope spanning the haemagglutinin cleavage site of H7N9 subtype avian influenza virus for the differentiation of infected and vaccinated chickens.

Avian Pathol 2022 Aug 19;51(4):330-338. Epub 2022 Apr 19.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, People's Republic of China.

H7N9 subtype avian influenza virus (AIV) is endemic in poultry in China, and vaccination is used as the primary strategy for disease control. However, by current serological tests, monitoring H7N9 virus infection in vaccinated poultry is difficult because vaccine-induced antibodies are not readily distinguishable from field viruses. Therefore, a test differentiating infected and vaccinated animals (DIVA) is critical for monitoring H7N9 virus. However, no DIVA test is available for the H7N9 subtype AIV. This study investigated the potential of an epitope (peptide 11) spanning the haemagglutinin (HA) cleavage site as a DIVA antigen for the H7N9 virus. The results showed that the H7N9 virus infection sera and post-challenge sera obtained from H7N9-vaccinated chickens reacted with peptide 11, whereas the sera elicited by inactivated and viral-vectored H7N9 vaccines had no reactivity with this peptide. Peptide 11 was further split into two peptides at the HA cleavage site, and the truncated peptides failed to discriminate H7N9 infected and vaccinated chickens. Peptide 11 is located in a main surface loop in the HA protein, and contains highly conserved residues in the HA cleavage site among the H7N9 subtype and different subtypes of groups 1 and 2, suggesting the potential of this peptide as a broad DIVA antigen for influenza viruses. Our study highlighted that peptide 11 is a promising DIVA antigen, and serological tests based on this peptide may serve as useful tools for monitoring H7N9 virus infection in vaccinated poultry. RESEARCH HIGHLIGHTSThe epitope spanning the HA cleavage site is a potential DIVA antigen for H7N9 AIV.The epitope reacted with LP and HP H7N9 viruses.The epitope has potential as a broad DIVA antigen for influenza viruses.
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http://dx.doi.org/10.1080/03079457.2022.2054308DOI Listing
August 2022

Generation of an avian influenza DIVA vaccine with a H3-peptide replacement located at HA2 against both highly and low pathogenic H7N9 virus.

Virulence 2022 12;13(1):530-541

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

A differentiating infected from vaccinated animals (DIVA) vaccine is an ideal strategy for viral eradication in poultry. Here, according to the emerging highly pathogenic H7N9 avian influenza virus (AIV), a DIVA vaccine strain, named rGD4-TX, was successfully developed, based on a substituted 12 peptide of H3 virus located at HA2. In order to meet with the safety requirement of vaccine production, the multi-basic amino acid located at the HA cleavage site was modified. Meanwhile, six inner viral genes from a H9N2 AIV TX strainwere introduced for increasing viral production. The rGD4-TX strain displayed a similar reproductive ability with rGD4 and low pathogenicity in chickens, suggesting a good productivity and safety. In immuned chickens, rGD4-TX induced a similar antibody level with rGD4 and provided 100% clinical protection and 90% shedding protection against highly pathogenic virus challenge. rGD4-TX strain also produced a good cross-protection against low pathogenic AIV JD/17. Moreover, serological DIVA characteristics were evaluated by a successfully established competitive inhibition ELISA based on a 3G10 monoclonal antibody, and the result showed a strong reactivity with antisera of chickens vaccinated with H7 subtype strains but not rGD4-TX. Collectedly, rGD4-TX is a promising DIVA vaccine candidate against both high and low pathogenic H7N9 subtype AIV.
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http://dx.doi.org/10.1080/21505594.2022.2040190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928850PMC
December 2022

Atomic-Layered Cu Nanoclusters on FeS with Dual Catalytic Sites for Efficient and Selective H O Activation.

Angew Chem Int Ed Engl 2022 May 21;61(21):e202200670. Epub 2022 Mar 21.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Institute of Applied & Environmental Chemistry, College of Chemistry, Central China Normal University, Wuhan, 430079, P. R. China.

Regulating the distribution of reactive oxygen species generated from H O activation is the prerequisite to ensuring the efficient and safe use of H O in the chemistry and life science fields. Herein, we demonstrate that constructing a dual Cu-Fe site through the self-assembly of single-atomic-layered Cu nanoclusters onto a FeS surface achieves selective H O activation with high efficiency. Unlike its unitary Cu or Fe counterpart, the dual Cu-Fe sites residing at the perimeter zone of the Cu /FeS interface facilitate H O adsorption and barrierless decomposition into ⋅OH via forming a bridging Cu-O-O-Fe complex. The robust in situ formation of ⋅OH governed by this atomic-layered catalyst enables the effective oxidation of several refractory toxic pollutants across a broad pH range, including alachlor, sulfadimidine, p-nitrobenzoic acid, p-chlorophenol, p-chloronitrobenzene. This work highlights the concept of building a dual catalytic site in manipulating selective H O activation on the surface molecular level towards efficient environmental control and beyond.
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http://dx.doi.org/10.1002/anie.202200670DOI Listing
May 2022

H5N1 infection impairs the alveolar epithelial barrier through intercellular junction proteins via Itch-mediated proteasomal degradation.

Commun Biol 2022 03 1;5(1):186. Epub 2022 Mar 1.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.

The H5N1 subtype of the avian influenza virus causes sporadic but fatal infections in humans. H5N1 virus infection leads to the disruption of the alveolar epithelial barrier, a pathologic change that often progresses into acute respiratory distress syndrome (ARDS) and pneumonia. The mechanisms underlying this remain poorly understood. Here we report that H5N1 viruses downregulate the expression of intercellular junction proteins (E-cadherin, occludin, claudin-1, and ZO-1) in several cell lines and the lungs of H5N1 virus-infected mice. H5N1 virus infection activates TGF-β-activated kinase 1 (TAK1), which then activates p38 and ERK to induce E3 ubiquitin ligase Itch expression and to promote occludin ubiquitination and degradation. Inhibition of the TAK1-Itch pathway restores the intercellular junction structure and function in vitro and in the lungs of H5N1 virus-infected mice. Our study suggests that H5N1 virus infection impairs the alveolar epithelial barrier by downregulating the expression of intercellular junction proteins at the posttranslational level.
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http://dx.doi.org/10.1038/s42003-022-03131-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888635PMC
March 2022

Oxygen and Chlorine Dual Vacancies Enable Photocatalytic O Dissociation into Monatomic Reactive Oxygen on BiOCl for Refractory Aromatic Pollutant Removal.

Environ Sci Technol 2022 03 24;56(6):3587-3595. Epub 2022 Feb 24.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Institute of Environmental Chemistry, Central China Normal University, Wuhan 430079, China.

Room-temperature molecular oxygen (O) dissociation is challenging toward chemical reactions due to its triplet ground-state and spin-forbidden characteristic. Herein, we demonstrate that BiOCl of oxygen and chlorine dual vacancies can photocatalytically dissociate O into monatomic reactive oxygen (•O) for the ring opening of aromatic refractory pollutants toward deep oxidation. The electron-rich and geometry-flexible dual vacancies of oxygen and chlorine remarkably lengthen the O-O bond of adsorbed O from 1.21 to 2.74 Å, resulting in the rapid O dissociation and the subsequent •O formation. During the photocatalytic degradation of sulfamethazine, the -formed •O plays an indispensable role in breaking the critical intermediate of pyrimidine containing a stubborn aromatic heterocyclic ring, thus facilitating the overall mineralization. More importantly, BiOCl of oxygen and chlorine dual vacancies is also superior to its monovacancy counterparts on the degradation of other refractory pollutants containing conjugated six-membered rings, including -chlorophenol, -chloronitrobenzene, -hydroxybenzoic acid, and -nitrobenzoic acid. This study sheds light on the importance of sophisticated defects for regulating the O activation manner and deliveries a novel O activation approach for environmental remediation with solar energy.
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http://dx.doi.org/10.1021/acs.est.1c08532DOI Listing
March 2022

[Characterization of a monoclonal antibody against the hemagglutinin stem of H7N9 subtype avian influenza virus].

Sheng Wu Gong Cheng Xue Bao 2022 Jan;38(1):160-173

Key Laboratory of Animal Infectious Diseases, School of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China.

The conserved hemagglutinin (HA) stem region of avian influenza virus (AIV) is an important target for designing broad-spectrum vaccines, therapeutic antibodies and diagnostic reagents. Previously, we obtained a monoclonal antibody (mAb) (5D3-1B5) which was reactive with the HA stem epitope (aa 428-452) of H7N9 subtype AIV. To systematically characterize the mAb, we determined the antibody titers, including the HA-binding IgG, hemagglutination-inhibition (HI) and virus neutralizing (VN) titers. In addition, the antigenic epitope recognized by the antibody as well as the sequence and structure of the antibody variable region (VR) were also determined. Moreover, we evaluated the cross-reactivity of the antibody with influenza virus strains of different subtypes. The results showed that the 5D3-1B5 antibody had undetectable HI and VN activities against H7N9 virus, whereas it exhibited strong reactivity with the HA protein. Using the peptide-based enzyme-linked immunosorbent assay and biopanning with a phage-displayed random peptide library, a motif with the core sequence (W-Y-L) in the C-helix domain in the HA stem was identified as the epitope recognized by 5D3-1B5. Moreover, the mAb failed to react with the mutant H7N9 virus which contains mutations in the epitope. The VR of the antibody was sequenced and the complementarity determining regions in the VR of the light and heavy chains were determined. Structural modeling and molecular docking analysis of the VR verified specific binding between the antibody and the C-helix domain of the HA stem. Notably, 5D3-1B5 showed a broad cross-reactivity with influenza virus strains of different subtypes belonging to groups 1 and 2. In conclusion, 5D3-1B5 antibody is a promising candidate in terms of the development of broad-spectrum virus diagnostic reagents and therapeutic antibodies. Our findings also provided new information for understanding the epitope characteristics of the HA protein of H7N9 subtype AIV.
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http://dx.doi.org/10.13345/j.cjb.210173DOI Listing
January 2022

Effects of HA2 154 deglycosylation and NA V202I mutation on biological property of H5N6 subtype avian influenza virus.

Vet Microbiol 2022 Mar 22;266:109353. Epub 2022 Jan 22.

Animal Infectious Diseases Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009, China; Jiangsu Key Laboratory of Zoonoses, Yangzhou University, Yangzhou, Jiangsu, 225009, China. Electronic address:

In recent years, clade 2.3.4.4 H5N6 subtype avian influenza virus (AIV) has been predominantly prevalent in poultry flocks in China. During our AIV surveillance in 2018-2019, 6 circulating strains of H5N6 that possess the natural loss of glycosylation site 154 due to N154D mutation in HA2 protein were isolated. In particular, 5 strains simultaneously carried the V202I mutation in NA protein. Based on the paired backbone H5N6 viruses Y6 and RY6, which just diverged in the glycosylation status at site 158 in HA1 protein, 8 reassortants of rY6-154 N/202 V, rY6-154D/202 V, rY6-154 N/202I and rY6-154D/202I plus rRY6-154 N/202 V, rRY6-154D/202 V, rRY6-154 N/202I and rRY6-154D/202I were constructed with different variation patterns at site 154 in HA2 and site 202 in NA. By determining those reassortants in growth performance on cells, plaque-forming ability, heat and low pH stability, and pathogenicity in mammals, the results showed that HA2 N154D and NA V202I could singly or jointly change the viral biological properties both in vitro and in vivo. Additionally, the effect of HA mutation was significantly more robust than that of NA, and the resulting increasing or reducing impact was closely related to the glycosylation at HA1 site 158. The present study provided a reference for further parsing the relevant mechanism of the functional match between HA and NA proteins of the influenza virus.
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http://dx.doi.org/10.1016/j.vetmic.2022.109353DOI Listing
March 2022

Expression and characterization of a recombinant broadly-reactive monoclonal antibody against group 1 and 2 influenza viruses.

Protein Expr Purif 2022 04 8;192:106046. Epub 2022 Jan 8.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China; Key Laboratory of Animal Infectious Diseases, School of Veterinary Medicine, Yangzhou University, Yangzhou, China. Electronic address:

Production of broadly-reactive antibodies is critical for universal immunodiagnosis of rapidly-evolving influenza viruses. Most monoclonal antibodies (mAbs) are generated in mice using the hybridoma technology which involves labor- and time-consuming screening and low yield issues. In this study, a recombinant antibody based on a broadly-reactive mAb against the hemagglutinin (HA) stalk of H7N9 avian influenza virus was expressed in CHO cells and its biological characteristics, cross-reactivity and epitope recognition were identified. The variable genes of the parental antibody were amplified and cloned into the antibody-expressing plasmids containing the constant genes of murine IgG1. The recombinant antibody was expressed in high yield and purity in CHO cells and showed similar features to the parental antibody, including negative hemagglutination inhibition activity against H7N9 virus and high binding activity with the H7N9 HA protein. Notably, the recombinant antibody exhibited a broad reactivity with different influenza subtypes belonging to group 1 and group 2, which was associated with its recognition of a highly-conserved epitope in the stalk, as observed for the parental antibody. Our results suggest that cell-based antibody expression system can be utilized as an important alternative to the hybridoma technology for antibody production for influenza virus diagnostics.
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http://dx.doi.org/10.1016/j.pep.2022.106046DOI Listing
April 2022

Phylogenetic and phenotypic characterization of two novel clade 2.3.2.1 H5N2 subtype avian influenza viruses from chickens in China.

Infect Genet Evol 2022 03 5;98:105205. Epub 2022 Jan 5.

Animal Infectious Diseases Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China. Electronic address:

The extended co-circulation of H5 subtype highly pathogenic avian influenza (HPAI) viruses and H9N2 low pathogenic avian influenza (LPAI) viruses has inevitably facilitated gene reassortment between the two subtypes in fields. And, novel reassortant H5NX viruses harboring partial or even whole sets of H9N2 internal genes have continuously been detected, such as clade 2.3.4.4 H5N2 or H5N6 reassortants. Here, we report two novel H5N2 subtype HPAI isolates of HF9 and QY5 from chickens in live poultry markets during routine surveillance in 2018. Phylogenetic analysis showed that those two H5N2 strains both possessed the HA genes from clade 2.3.2.1e of H5N1 viruses but all the other seven gene segments consistently from the endemic S genotype of H9N2 subtype viruses. Further analysis revealed that HF9 and QY5 differed only in six sites including K353R, A588T and T661I in PB2, I682V and L704S in PB1 plus G631S in PA at the amino acid level. A chicken regression experiment confirmed that both HF9 and QY5 were lethal infection to all tested chickens via contact transmission. Moreover, those two isolates could immediately replicate in mice lungs without adaptation. However, mortality rate of those two variants were distinct in mice model, HF9 with 100% but QY5 with just 20% at the infection dosage of 10EID per mouse. We suppose that the phenotypic difference may probably be attributed to the amino acid substitutions in the polymerase genes between the two isolates that constitute of a subject of further ongoing research.
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http://dx.doi.org/10.1016/j.meegid.2022.105205DOI Listing
March 2022

Spatiotemporal Associations and Molecular Evolution of Highly Pathogenic Avian Influenza A H7N9 Virus in China from 2017 to 2021.

Viruses 2021 12 15;13(12). Epub 2021 Dec 15.

Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Highly pathogenic (HP) H7N9 avian influenza virus (AIV) emerged in China in 2016. HP H7N9 AIV caused at least 33 human infections and has been circulating in poultry farms continuously since wave 5. The genetic divergence, geographic patterns, and hemagglutinin adaptive and parallel molecular evolution of HP H7N9 AIV in China since 2017 are still unclear. Here, 10 new strains of HP H7N9 AIVs from October 2019 to April 2021 were sequenced. We found that HP H7N9 was primarily circulating in Northern China, particularly in the provinces surrounding the Bohai Sea (Liaoning, Hebei, and Shandong) since wave 6. Of note, HP H7N9 AIV phylogenies exhibit a geographical structure compatible with high levels of local transmission after unidirectional rapid geographical expansion towards the north of China in 2017. In addition, we showed that two major subclades were continually expanding with the viral population size undergoing a sharp increase after 2018 with an obvious seasonal tendency. Notably, the hemagglutinin gene showed signs of parallel evolution and positive selection. Our research sheds light on the current epidemiology, evolution, and diversity of HP H7N9 AIV that can help prevent and control the spreading of HP H7N9 AIV.
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http://dx.doi.org/10.3390/v13122524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705967PMC
December 2021

Genome-Wide Analysis of Alternative Splicing during Host-Virus Interactions in Chicken.

Viruses 2021 12 2;13(12). Epub 2021 Dec 2.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

The chicken is a model animal for the study of evolution, immunity and development. In addition to their use as a model organism, chickens also represent an important agricultural product. Pathogen invasion has already been shown to modulate the expression of hundreds of genes, but the role of alternative splicing in avian virus infection remains unclear. We used RNA-seq data to analyze virus-induced changes in the alternative splicing of Gallus gallus, and found that a large number of alternative splicing events were induced by virus infection both in vivo and in vitro. Virus-responsive alternative splicing events preferentially occurred in genes involved in metabolism and transport. Many of the alternatively spliced transcripts were also expressed from genes with a function relating to splicing or immune response, suggesting a potential impact of virus infection on pre-mRNA splicing and immune gene regulation. Moreover, exon skipping was the most frequent AS event in chickens during virus infection. This is the first report describing a genome-wide analysis of alternative splicing in chicken and contributes to the genomic resources available for studying host-virus interaction in this species. Our analysis fills an important knowledge gap in understanding the extent of genome-wide alternative splicing dynamics occurring during avian virus infection and provides the impetus for the further exploration of AS in chicken defense signaling and homeostasis.
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http://dx.doi.org/10.3390/v13122409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703359PMC
December 2021

Baculovirus-derived influenza virus-like particle confers complete protection against lethal H7N9 avian influenza virus challenge in chickens and mice.

Vet Microbiol 2022 Jan 14;264:109306. Epub 2021 Dec 14.

Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. Electronic address:

Currently, highly pathogenic avian influenza (HPAI) H7N9 viruses still pose a potential pandemic threat. Influenza virus-like particle (VLP) is one of the most promising vaccine strategies to complement traditional egg-dependent vaccines. Here, we generated a H7N9 VLP vaccine candidate by baculovirus expression system and evaluated its efficacy in chickens and mice. The H7N9 VLP was produced through co-infection of Sf9 insect cells with three recombinant baculoviruses expressing individual HA, NA and M1 gene of the HPAI H7N9 virus A/chicken/Guangdong/GD15/2016. Intramuscular immunization of the H7N9 VLP elicited robust antibody immune responses and conferred complete clinical protection against lethal H7N9 virus challenge both in chickens and mice. Meanwhile, H7N9 VLP significantly restrained virus shedding and dramatically alleviated pulmonary lesions caused by H7N9 virus infection in birds and mice. Interestingly, chicken antibodies induced by the H7N9 VLP also had a good cross-reactivity with H7N9 field strains isolated in different years. In addition, vaccination with the H7N9 VLP elicited high T cell immunity in mouse lung, evidenced by significantly upregulated expression of IL-2, IL-4 and IFN-γ. Furthermore, the H7N9 VLP significantly decreased the expression of some key inflammatory cytokines, such as IL6, RANTES and TNF-α in mouse lung, which may partially account for its contribution to alleviate lung pathology. Therefore, our study describes the good efficacy of the HA + NA + M1-containing H7N9 VLP both in chicken and mice models, highlighting the potential of VLP-based vaccine as a critical alternative of traditional egg-based vaccine for control of H7N9 influenza virus in both humans and poultry.
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http://dx.doi.org/10.1016/j.vetmic.2021.109306DOI Listing
January 2022

Single Dose of Bivalent H5 and H7 Influenza Virus-Like Particle Protects Chickens Against Highly Pathogenic H5N1 and H7N9 Avian Influenza Viruses.

Front Vet Sci 2021 11;8:774630. Epub 2021 Nov 11.

Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Both H5N1 and H7N9 subtype avian influenza viruses cause enormous economic losses and pose considerable threats to public health. Bivalent vaccines against both two subtypes are more effective in control of H5N1 and H7N9 viruses in poultry and novel egg-independent vaccines are needed. Herein, H5 and H7 virus like particle (VLP) were generated in a baculovirus expression system and a bivalent H5+H7 VLP vaccine candidate was prepared by combining these two antigens. Single immunization of the bivalent VLP or commercial inactivated vaccines elicited effective antibody immune responses, including hemagglutination inhibition, virus neutralizing and HA-specific IgG antibodies. All vaccinated birds survived lethal challenge with highly pathogenic H5N1 and H7N9 viruses. Furthermore, the bivalent VLP significantly reduced viral shedding and virus replication in chickens, which was comparable to that observed for the commercial inactivated vaccine. However, the bivalent VLP was better than the commercial vaccine in terms of alleviating pulmonary lesions caused by H7N9 virus infection in chickens. Therefore, our study suggests that the bivalent H5+H7 VLP vaccine candidate can serve as a critical alternative for the traditional egg-based inactivated vaccines against H5N1 and H7N9 avian influenza virus infection in poultry.
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http://dx.doi.org/10.3389/fvets.2021.774630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632145PMC
November 2021

Biological Characterization and Evolutionary Dynamics of Pigeon Paramyxovirus Type 1 in China.

Front Vet Sci 2021 13;8:721102. Epub 2021 Oct 13.

Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Pigeon paramyxovirus type 1 (PPMV-1) is considered as an antigenic variant of Newcastle disease virus (NDV) which has an obvious host preference for pigeons and has caused significant economic losses to the global poultry industry. The evolutionary dynamics of PPMV-1 in China, however, are poorly understood. In this study, we characterized seven PPMV-1 isolates from diseased pigeons collected in Jiangsu, Anhui, and Henan provinces during 2020. Phylogenetic analysis revealed that seven isolates belonged to sub-genotype VI.2.1.1.2.2. Biological characterization indicated that seven isolates were mesogenic based on the mean death time (69.6-91.2 h) and intracerebral pathogenicity index (1.19-1.40) and had similar growth kinetics in chicken embryos and CEFs. Furthermore, the four representative viruses (AH/01/20/Pi, JS/06/20/Pi, HN/01/20/Pi, and HN/02/20/Pi) could result in marked cytopathic effects (CPE) in CEFs and induced syncytium formation in Vero cells. Our Bayesian phylogenetic analysis showed that PPMV-1 might first emerge in East China in 1974 and East China had the highest genotypic diversity of PPMV-1. Besides, phylogeographic analysis indicated that East China and South China were probably the major epicenters of dissemination of PPMV-1 in China. Selection pressure analysis and amino acid substitutions analysis revealed that the viral replication complex (NP, P, and L proteins) was likely related with the host preference of PPMV-1. Collectively, this study uncovered the epidemiology and evolutionary dynamics of PPMV-1 circulating in China, emphasizing the importance of strengthening the monitoring of PPMV-1 in East China and South China and providing significant clues for further studies on the molecular mechanism underlying host preference of PPMV-1.
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http://dx.doi.org/10.3389/fvets.2021.721102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548471PMC
October 2021

Newcastle disease virus degrades SIRT3 via PINK1-PRKN-dependent mitophagy to reprogram energy metabolism in infected cells.

Autophagy 2022 07 31;18(7):1503-1521. Epub 2021 Oct 31.

Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, P.R. China.

Lacking a self-contained metabolism network, viruses have evolved multiple mechanisms for rewiring the metabolic system of their host to hijack the host's metabolic resources for replication. Newcastle disease virus (NDV) is a paramyxovirus, as an oncolytic virus currently being developed for cancer treatment. However, how NDV alters cellular metabolism is still far from fully understood. In this study, we show that NDV infection reprograms cell metabolism by increasing glucose utilization in the glycolytic pathway. Mechanistically, NDV induces mitochondrial damage, elevated mitochondrial reactive oxygen species (mROS) and ETC dysfunction. Infection of cells depletes nucleotide triphosphate levels, resulting in elevated AMP:ATP ratios, AMP-activated protein kinase (AMPK) phosphorylation, and MTOR crosstalk mediated autophagy. In a time-dependent manner, NDV shifts the balance of mitochondrial dynamics from fusion to fission. Subsequently, PINK1-PRKN-dependent mitophagy was activated, forming a ubiquitin chain with MFN2 (mitofusin 2), and molecular receptor SQSTM1/p62 recognized damaged mitochondria. We also found that NDV infection induces NAD-dependent deacetylase SIRT3 loss via mitophagy to engender HIF1A stabilization, leading to the switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Overall, these studies support a model that NDV modulates host cell metabolism through PINK1-PRKN-dependent mitophagy for degrading SIRT3. AMPK: AMP-activated protein kinase; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; ECAR: extracellular acidification rate; hpi: hours post infection LC-MS: liquid chromatography-mass spectrometry; mito-QC: mCherry-GFP-FIS1[mt101-152]; MFN2: mitofusin 2; MMP: mitochondrial membrane potential; mROS: mitochondrial reactive oxygen species; MOI: multiplicity of infection; 2-NBDG: 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose; NDV: newcastle disease virus; OCR: oxygen consumption rate; siRNA: small interfering RNA; SIRT3: sirtuin 3; TCA: tricarboxylic acid; TCID: tissue culture infective doses.
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http://dx.doi.org/10.1080/15548627.2021.1990515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298456PMC
July 2022

Ubiquitination on Lysine 247 of Newcastle Disease Virus Matrix Protein Enhances Viral Replication and Virulence by Driving Nuclear-Cytoplasmic Trafficking.

J Virol 2022 01 27;96(2):e0162921. Epub 2021 Oct 27.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, People's Republic of China.

The Newcastle disease virus (NDV) matrix (M) protein is the pivotal element for viral assembly, budding, and proliferation. It traffics through the cellular nucleus but performs its primary function in the cytoplasm. To investigate the biological importance of M protein nuclear-cytoplasmic trafficking and the mechanism involved, the regulatory motif nuclear export signal (NES) and nuclear localization signal (NLS) were analyzed. Here, two types of combined NLSs and NESs were identified within the NDV-M protein. The Herts/33-type M protein was found to mediate efficient nuclear export and stable virus-like particle (VLP) release, while the LaSota-type M protein was retained mostly in the nuclei and showed retarded VLP production. Two critical residues, namely, 247 and 263, within the motif were identified and associated with nuclear export efficiency. We identified, for the first time, residue 247 as an important monoubiquitination site, of which its modification regulates the nuclear-cytoplasmic trafficking of NDV-M. Subsequently, mutant LaSota strains were rescued via reverse genetics, which contained either single or double amino acid substitutions that were similar to the M of Herts/33. The rescued LaSota (rLaSota) strains rLaSota-R247K, -S263R, and -double mutation (DM) showed about 2-fold higher hemagglutination (HA) titers and 10-fold higher 50% egg infective dose (EID) titers than wild-type (wt) rLaSota. Furthermore, the mean death time (MDT) and intracerebral pathogenicity index (ICPI) values of those recombinant viruses were slightly higher than those of wt rLaSota probably due to their higher proliferation rates. Our findings contribute to a better understanding of the molecular mechanism of the replication and pathogenicity of NDV and even those of all other paramyxoviruses. This information is beneficial for the development of vaccines and therapies for paramyxoviruses. Newcastle disease virus (NDV) is a pathogen that is lethal to birds and causes heavy losses in the poultry industry worldwide. The World Organization for Animal Health (OIE) ranked Newcastle disease (ND) as the third most significant poultry disease and the eighth most important wildlife disease in the World Livestock Disease Atlas in 2011. The matrix (M) protein of NDV is very important for viral assembly and maturation. It is interesting that M proteins enter the cellular nucleus before performing their primary function in the cytoplasm. We found that NDV-M has a combined nuclear import and export signal. The ubiquitin modification of a lysine residue within this signal is critical for quick, efficient nuclear export and subsequent viral production. Our findings shed new light on viral replication and open up new possibilities for therapeutics against NDV and other paramyxoviruses; furthermore, we demonstrate a novel approach for improving paramyxovirus vaccines.
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http://dx.doi.org/10.1128/JVI.01629-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791254PMC
January 2022

Van Der Waals gap-rich BiOCl atomic layers realizing efficient, pure-water CO-to-CO photocatalysis.

Nat Commun 2021 Oct 11;12(1):5923. Epub 2021 Oct 11.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Institute of Environmental & Applied Chemistry, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, China.

Photocatalytic CO reduction (PCR) is able to convert solar energy into chemicals, fuels, and feedstocks, but limited by the deficiencies of photocatalysts in steering photon-to-electron conversion and activating CO, especially in pure water. Here we report an efficient, pure water CO-to-CO conversion photocatalyzed by sub-3-nm-thick BiOCl nanosheets with van der Waals gaps (VDWGs) on the two-dimensional facets, a graphene-analog motif distinct from the majority of previously reported nanosheets usually bearing VDWGs on the lateral facets. Compared with bulk BiOCl, the VDWGs-rich atomic layers possess a weaker excitonic confinement power to decrease exciton binding energy from 137 to 36 meV, consequently yielding a 50-fold enhancement in the bulk charge separation efficiency. Moreover, the VDWGs facilitate the formation of VDWG-Bi-V-Bi defect, a highly active site to accelerate the CO-to-CO transformation via the synchronous optimization of CO activation, *COOH splitting, and *CO desorption. The improvements in both exciton-to-electron and CO-to-CO conversions result in a visible light PCR rate of 188.2 μmol g h in pure water without any co-catalysts, hole scavengers, or organic solvents. These results suggest that increasing VDWG exposure is a way for designing high-performance solar-fuel generation systems.
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http://dx.doi.org/10.1038/s41467-021-26219-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505634PMC
October 2021

Development of an Inactivated H7N9 Subtype Avian Influenza Serological DIVA Vaccine Using the Chimeric HA Epitope Approach.

Microbiol Spectr 2021 10 29;9(2):e0068721. Epub 2021 Sep 29.

College of Veterinary Medicine, Yangzhou Universitygrid.268415.c, Yangzhou, Jiangsu, China.

H7N9 avian influenza virus (AIV) is an emerging zoonotic pathogen, and it is necessary to develop a ifferentiating nfected from accinated nimals (DIVA) vaccine for the purpose of eradication. H7N9 subtype AIV hemagglutinin subunit 2 glycoprotein (HA2) peptide chips and antisera of different AIV subtypes were used to screen H7N9 AIV-specific epitopes. A selected specific epitope in the HA2 protein of H7N9 AIV strain A/Chicken/Huadong/JD/17 (JD/17) was replaced with an epitope from an H3N2 subtype AIV strain by reverse genetics. The protection and serological DIVA characteristics of the recombinant H7N9 AIV strain were evaluated. The results showed that a specific epitope on the HA2 protein of H7N9 AIV, named the H7-12 peptide, was successfully screened. The recombinant H7N9 AIV with a modified epitope in the HA2 protein was rescued and named A/Chicken/Huadong/JD-cHA/17 (JD-cHA/17). The HA titer of JD-cHA/17 was 10 log, and the 50% egg infective dose (EID) titer was 9.67 log EID/ml. Inactivated JD-cHA/17 induced a hemagglutination inhibition (HI) antibody titer similar that of the parent strain and provided 100% protection against high-pathogenicity or low-pathogenicity H7N9 AIV challenge. A peptide chip coated with H7-12 peptide was successfully applied to detect the seroconversion of chickens infected or vaccinated with JD/17, while there was no reactivity with antisera of chickens vaccinated with JD-cHA/17. Therefore, the marked vaccine candidate JD-cHA/17 can be used as a DIVA vaccine against H7N9 avian influenza when combined with an H7-12 peptide chip, making it a useful tool for stamping out the H7N9 AIV. DIVA vaccine is a useful tool for eradicating avian influenza, especially for highly pathogenic avian influenza. Several different DIVA strategies have been proposed for avian influenza inactivated whole-virus vaccine, involving the neuraminidase (NA), nonstructural protein 1 (NS1), matrix protein 2 ectodomain (M2e), or HA2 gene. However, virus reassortment, residual protein in a vaccine component, or reduced vaccine protection may limit the application of these DIVA strategies. Here, we constructed a novel chimeric H7N9 AIV, JD-cHA/17, that expressed the entire HA protein with substitution of an H3 AIV epitope in HA2. The chimeric H7N9 recombinant vaccine provides full clinical protection against high-pathogenicity or low-pathogenicity H7N9 AIV challenge. Combined with a short-peptide-based microarray chip containing the H7N9 AIV epitope in HA2, our finding is expected to be useful as a marker vaccine designed for avian influenza.
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http://dx.doi.org/10.1128/Spectrum.00687-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557892PMC
October 2021

Efficient removal of PFOA with an InO/persulfate system under solar light via the combined process of surface radicals and photogenerated holes.

J Hazard Mater 2022 02 12;423(Pt B):127176. Epub 2021 Sep 12.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Institute of Environmental & Applied Chemistry, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, PR China. Electronic address:

The environmental persistence, high toxicity and wide spread presence of perfluorooctanoic acid (PFOA) in aquatic environment urgently necessitate the development of advanced technologies to eliminate PFOA. Here, the simultaneous application of a heterogeneous InO photocatalyst and homogeneous persulfate oxidation (InO/PS) was demonstrated for PFOA degradation under solar light irradiation. The synergistic effect of direct hole oxidation and in-situ generated radicals, especially surface radicals, was found to contribute significantly to PFOA defluorination. Fourier infrared transform (FTIR) spectroscopy, Raman, electrochemical scanning microscope (SECM) tests and density functional theory (DFT) calculation showed that the pre-adsorption of PFOA and PS onto InO surface were dramatically critical steps, which could efficiently facilitate the direct hole oxidation of PFOA, and boost PS activation to yield high surface-confined radicals, thus prompting PFOA degradation. Response surface methodology (RSM) was applied to regulate the operation parameters for PFOA defluorination. Outstanding PFOA decomposition (98.6%) and near-stoichiometric equivalents of fluorides release were achieved within illumination 10 h. An underlying mechanism for PFOA destruction was proposed via a stepwise losing CF unit. The InO/PS remediation system under solar light provides an economical, sustainable and environmentally friendly approach for complete mineralization of PFOA, displaying a promising potential for treatment of PFOA-containing water.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127176DOI Listing
February 2022

Emergence of a novel reassortant avian influenza virus (H10N3) in Eastern China with high pathogenicity and respiratory droplet transmissibility to mammals.

Sci China Life Sci 2022 05 17;65(5):1024-1035. Epub 2021 Sep 17.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.

Decades have passed since the first discovery of H10-subtype avian influenza virus (AIV) in chickens in 1949, and it has been detected in many species including mammals such as minks, pigs, seals and humans. Cases of human infections with H10N8 viruses identified in China in 2013 have raised widespread attention. Two novel reassortant H10N3 viruses were isolated from chickens in December 2019 in eastern China during routine surveillance for AIVs. The internal genes of these viruses were derived from genotype S (G57) H9N2 and were consistent with H5N6, H7N9 and H10N8, which cause fatal infections in humans. Their viral pathogenicity and transmissibility were further studied in different animal models. The two H10N3 isolates had low pathogenicity in chickens and were transmitted between chickens via direct contact. These viruses were highly pathogenic in mice and could be transmitted between guinea pigs via direct contact and respiratory droplets. More importantly, these viruses can bind to both human-type SAα-2,6-Gal receptors and avian-type SAα-2,3-Gal receptors. Asymptomatic shedding in chickens and good adaptability to mammals of these H10N3 isolates would make it easier to transmit to humans and pose a threat to public health.
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http://dx.doi.org/10.1007/s11427-020-1981-5DOI Listing
May 2022

Adjacent single-atom irons boosting molecular oxygen activation on MnO.

Nat Commun 2021 Sep 14;12(1):5422. Epub 2021 Sep 14.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, 430079, Wuhan, P. R. China.

Efficient molecular oxygen activation is crucial for catalytic oxidation reaction, but highly depends on the construction of active sites. In this study, we demonstrate that dual adjacent Fe atoms anchored on MnO can assemble into a diatomic site, also called as MnO-hosted Fe dimer, which activates molecular oxygen to form an active intermediate species Fe(O = O)Fe for highly efficient CO oxidation. These adjacent single-atom Fe sites exhibit a stronger O activation performance than the conventional surface oxygen vacancy activation sites. This work sheds light on molecular oxygen activation mechanisms of transition metal oxides and provides an efficient pathway to activate molecular oxygen by constructing new active sites through single atom technology.
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http://dx.doi.org/10.1038/s41467-021-25726-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440510PMC
September 2021
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