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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

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Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li State Key Laboratory for animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

Small mammal community composition impacts bank vole (Clethrionomys glareolus) population dynamics and associated seroprevalence of Puumala orthohantavirus

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Integrative Zoology 2024年第1期19卷 52-65页

作者： Felicitas Maria BUJNOCH Daniela REIL Stephan DREWES Ulrike MROSENFELD Rainer G.ULRICH Jens JACOB Christian IMHOLT Julius Kühn-institute Federal Research Centre for Cultivated PlantsInstitute for Epidemiology and Pathogen DiagnosticsRodent ResearchMünsterGermany University of Münster Institute for Evolution and BiodiversityMünsterGermany Friedrich-Loeffler-Institut Federal Research Institute for Animal HealthInstitute of Novel and Emerging Infectious DiseasesGreifswald-Insel RiemsGermany

Rodents are important reservoirs for zoonotic pathogens that cause diseases in *** is hypoth-esized to be closely related to pathogen prevalence through multiple direct and indirect *** example,the presence of non-host species can reduce contact rates of the main reservoir host and thus reduce the risk of transmission(“dilution effect”).In addition,an overlap in ecological niches between two species could lead to increased interspecific competition,potentially limiting host densities and reducing density-dependent pathogen transmission *** this study,we investigated the relative impact of population-level regulation of direct and indirect drivers of the prevalence of Puumala orthohantavirus(PUUV)in bank voles(Clethrionomys glareolus)during years with high *** compiled data on small mammal community composition from four regions in Germany between 2010 and *** equation modeling revealed a strong seasonality in PUUV control mechanisms in bank *** abundance of shrews tended to have a negative relationship with host abundance,and host abundance positively influenced PUUV seroprevalence,while at the same time increasing the abundance of competing non-hosts like the wood mouse(Apodemus sylvaticus)and the yellow-neckedfield mouse(Apodemusflavicollis)were associated with reduced PUUV seroprevalence in the *** results indicate that for PUUV in bank voles,dilution is associated with increased interspecific *** pressures leading to the decline of Apodemus *** a specific habitat could lead to the amplification of mechanisms promoting PUUV transmission within the host populations.

关键词： bank vole biodiversity Puumala orthohantavirus small mammals

Establishment of a chicken intestinal organoid culture system to assess deoxynivalenol‑induced damage of the intestinal barrier function

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Journal of animal Science and Biotechnology 2024年第3期15卷 1119-1130页

作者： Tae Hong Kang Sang In Lee Department of animal Science and Biotechnology Kyungpook National UniversitySangjuGyeong‑Sangbuk‑Do 37224Republic of Korea research institute for Innovative animal Science Kyungpook National University37224SangjuGyeong‑Sangbuk‑DoRepublic of Korea

Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in *** DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small *** We established a culture system using chicken organoids and characterized the organoids at passages 1 and *** confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small *** results showed that the organoids displayed functional similarities in permeability compared to the small *** damaged the tight junctions of the organoids,which resulted in increased *** Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine *** on these similarities,we confirmed that DON causes small intestine *** organoids offer a practical model for the research of harmful substances.

关键词： Barrier function Deoxynivalenol Organoids

Control of highly pathogenic avian influenza through vaccination

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Journal of Integrative Agriculture 2024年第5期23卷 1447-1453页

作者： Xianying Zeng Jianzhong Shi Hualan Chen State Key Laboratory for animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China

The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to *** this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and *** addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.

关键词： avian influenza control highly pathogenic vaccination

Large-Scale CRISPR Screen of LDLR Pathogenic Variants

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research 2024年第2期2023卷 213-225页

作者： Mengjing Li Lerong Ma Yiwu Chen Jianing Li Yanbing Wang Wenni You Hongming Yuan Xiaochun Tang Hongsheng Ouyang Daxin Pang Key Lab for Zoonoses research Ministry of EducationAnimal Genome Editing Technology Innovation CenterCollege of Animal SciencesJilin UniversityChangchunJilin Province 130062China The institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300071China Chongqing researchinstitute Jilin UniversityChongqing 401123China Chongqing Jitang Biotechnology research institute Co.Ltd. ChongqingChina

Familial hypercholesterolemia(FH)is a frequently occurring genetic disorder that is linked to early-onset cardiovascular *** left untreated,patients with this condition can develop severe cardiovascular ***,many patients remain undiagnosed,and even when diagnosed,the treatment is often not *** mutations in the LDLR gene are the primary cause of FH,predicting whether novel variants are pathogenic is not a straightforward *** the functionality of LDLR variants is crucial in uncovering the genetic basis of *** study utilized CRISPR/Cas9 cytosine base editors in pooled screens to establish a novel approach for functionally assessing tens of thousands of LDLR variants on a large scale.A total of more than 100 single guide RNAs(sgRNAs)targeting LDLR pathogenic mutations were successfully screened with relatively high *** of these,5 sgRNAs were further subjected to functional verification studies,including 1 in the promoter,1 in the antisense RNA,1 in the exon,and 2 in the *** for the variant caused by the sgRNA located at intron 16,the functionalities of the other LDLR variants were all *** high similarity of LDLR intron sequences may lead to some false ***,these results confirm the reliability of the large-scale screening strategy for functional analysis of LDLR variants,and the screened candidate pathogenic mutations could be used as an auxiliary means of clinical gene detection to prevent FH-induced heart disease.

关键词： LDLR Screen straight

Ancient mitochondrial genome depicts sheep maternal dispersal and migration in Eastern Asia

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Journal of Genetics and Genomics 2024年第1期51卷 87-95页

作者： Liu Yang Xing Zhang Yaning Hu Piao Zhu Hua Li Zhenyu Peng Hai Xiang Xinying Zhou Xingbo Zhao National Engineering Laboratory for animal Breeding Key Laboratory of AnimalGeneticsBreeding and ReproductionMinistry of Agriculture and Rural AffairsCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Guangdong Provincial Key Laboratory of animal Molecular Design and Precise Breeding School of Life Science and EngineeringFoshan UniversityFoshanGuangdong 528225China State Key Laboratory of Agricultural Genomics BGI-ShenzhenShenzhenGuangdong 518083China Key Laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

Sheep have been one of the most important groups of animals since ancient ***,the knowledge of their migration routes and genetic relationships is still poorly *** investigate sheep maternal migration histories alongside Eurasian communications routes,in this study,we obtain mitochondrial genomes(mitogenomes)from 17 sheep remains in 6 Chinese sites and 1 Uzbekistan site dated 4429–3100 years before present(BP).By obtaining the mitogenomes from the sheep(4429–3556 BP)found in the Tongtian Cave site in Xinjiang,Altai region of northwest China,our results support the emergence of haplogroup C sheep in Xinjiang as early as 4429–3556 *** combined phylogenetic analyses with extant ancient and modern sheep mitogenomes suggest that the Uzbekistan-Altai region may have been a migration hub for early sheep in eastern *** least two migration events have taken place for sheep crossing Eurasia to China,one passing by Uzbekistan and Northwest China to the middle and lower reaches of the Yellow River at approximately 4000 BP and another following the Altai region to middle Inner Mongolia from 4429 BP to 2500 ***,this study provides further evidence for early sheep utilization and migration patterns in Eastern Asia.

关键词： Sheep Ancient DNA Eastern Asia Mitochondrial genome Migration Altai

Retinoic acid alleviates rotavirus-induced intestinal damage by regulating redox homeostasis and autophagic flux in piglets

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animal Nutrition 2024年第1期16卷 409-421页

作者： Xin Lai Aimin Wu Bing Yu Hui Yan Junqiu Luo Ping Zheng Jie Yu Daiwen Chen institute of animal Nutrition Sichuan Agricultural University Key Laboratory for animal Disease-resistance Nutrition of China Ministry of Education Sichuan Agricultural University

Rotaviruses(RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid(RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire(DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients(5and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA(5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio(P research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.

关键词： Rotavirus Piglet Retinoic acid Intestinal barrier Redox hemostasis Autophagic flux

KLF4 facilitates chromatin accessibility remodeling in porcine early embryos

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Science China(Life Sciences) 2024年第1期67卷 96-112页

作者： Wei Zhu Guowei Bu Ruifeng Hu Jixiang Zhang Lianyong Qiao Kai Zhou Tingting Wang Qiao Li Jingjing Zhang Linhui Wu Yali Xie Taotao Hu Shichun Yang Jiaqi Guan Xiaoyu Chu Juanjuan Shi Xia Zhang Falong Lu Xin Liu Yi-Liang Miao institute of Stem Cell and Regenerative Biology College of Animal Science and Veterinary MedicineHuazhong Agricultural UniversityWuhan 430070China Key Laboratory of Agricultural animal Genetics Breeding and Reproduction(Huazhong Agricultural University)Ministry of EducationWuhan 430070China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyInnovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China Frontiers Science Center for animal Breeding and Sustainable Production Huazhong Agricultural UniversityWuhan 430070China Hubei Hongshan Laboratory Wuhan 430070China

Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early *** studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not *** employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation *** data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early *** down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine ***,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine *** addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this *** together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.

关键词： porcine embryos liDNase-seq chromatin accessibility KLF4 mitochondrion lipid droplets

Transcriptome-based analysis of key signaling pathways affecting the formation of primordial germ cell in chickens

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Journal of Integrative Agriculture 2024年第5期23卷 1644-1657页

作者： Ying Ding Qiong Zhi Qisheng Zuo Kai Jin Wei Han Bichun Li Key Laboratory of animal Genetics Breeding and Molecular Design of Jiangsu ProvinceCollege of Animal Science and TechnologyYangzhou UniversityYangzhou 225009China Joint International research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China Yangzhou UniversityYangzhou225009China Poultry research institute Chinese Academy of Agricultural Sciences/Jiangsu Institute of Poultry ScienceYangzhou 225009China

Bone morphogenetic protein 4(BMP4)can induce the formation of chicken primordial germ cells(PGCs)in vitro;however,its regulatory mechanism in poultry remains *** study aimed to use RNA-seq to analyze PGCs in chicken embryos and iPGCs induced by BMP4 in vitro,clarify the internal regulatory factors of PGCs,analyze the mechanism of the formation of PGCs,and lay a theoretical foundation for the further optimization of PGCs induction *** stem cells(ESCs),PGCs and iPGCs induced by BMP4 in vitro were *** transcriptional maps of the three cell types were studied using *** results showed 6,142 genes differentially expressed between PGCs and iPGCs,of which 2,728 were upregulated in iPGCs and 3,414 were downregulated in *** to that in ESCs,BMP4 was significantly upregulated in PGCs and *** results showed that both the TGF-βand Wnt signaling pathways were activated during the formation of PGCs in vitro and in vivo,and the activation was more significant during iPGCs induced by *** expression of Nodal,an inhibitory factor of TGF-βsignaling,was significantly decreased in PGCs and iPGCs,but was not expressed in iPGCs,which further supports our ***,the Lysosome and PI3K-AKT signaling pathways were significantly enriched in PGCs and iPGCs,***,transmission electron microscopy(TEM)results showed that the number of autolysosomes was significantly higher after the addition of BMP4,which is consistent with the KEGG ***,the number of PGCs was significantly reduced after ATG14 was interfered in vivo and in *** conclusion,this study screened out the key signaling pathways during the formation of PGCs,aiming to provide help for enriching the mechanism network regulating PGCs formation in chicken and laying a theoretical foundation for further improving the efficiency of inducing PGCs in vitro.

关键词： RNA-seq BMP4 PGCs ATG14 chicken