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Engineered AAV13 variants with enhanced transduction and confined spread. 工程化 AAV13 变体,可增强转导和限制传播。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2023.355
Neng-Song Luo, Yu-Xiang Cai, Zeng-Peng Han, Xiao-Kai Sui, Wen-Jia Yuan, Zi-Lian Zhang, Hao-Dong Guo, Jie Wang, Kun-Zhang Lin, Fu-Qiang Xu
{"title":"Engineered AAV13 variants with enhanced transduction and confined spread.","authors":"Neng-Song Luo, Yu-Xiang Cai, Zeng-Peng Han, Xiao-Kai Sui, Wen-Jia Yuan, Zi-Lian Zhang, Hao-Dong Guo, Jie Wang, Kun-Zhang Lin, Fu-Qiang Xu","doi":"10.24272/j.issn.2095-8137.2023.355","DOIUrl":"10.24272/j.issn.2095-8137.2023.355","url":null,"abstract":"<p><p>Precise targeting of specific regions within the central nervous system (CNS) is crucial for both scientific research and gene therapy in the context of brain diseases. Adeno-associated virus 13 (AAV13) is known for its restricted diffusion range within the CNS, making it an ideal choice for precise labeling and administration within small brain regions. However, AAV13 mediates relatively low expression of target genes. Here, we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency. We first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid. We then inserted the 7m8 peptide, known to enhance cell transduction, into positions 587/588 and 585/586 of the AAV13 capsid, resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8, respectively. We found that AAV13-YF exhibited superior <i>in vitro</i> infectivity in HEK293T cells compared to AAV13, while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice, with AAV13-587-7m8 infection retaining a limited spread range. These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microplastic exposure disturbs sleep structure, reduces lifespan, and decreases ovary size in Drosophila melanogaster. 接触微塑料会扰乱黑腹果蝇的睡眠结构、缩短其寿命并缩小其卵巢体积。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.038
Wei Yan, Zi-Jie Li, Zi-Yi Lin, Shu-Qin Ji, William Ka Fai Tse, Zhi-Qiang Meng, Chang Liu, Lei Li
{"title":"Microplastic exposure disturbs sleep structure, reduces lifespan, and decreases ovary size in <i>Drosophila</i> <i>melanogaster</i>.","authors":"Wei Yan, Zi-Jie Li, Zi-Yi Lin, Shu-Qin Ji, William Ka Fai Tse, Zhi-Qiang Meng, Chang Liu, Lei Li","doi":"10.24272/j.issn.2095-8137.2024.038","DOIUrl":"10.24272/j.issn.2095-8137.2024.038","url":null,"abstract":"<p><p>The organ-specific toxicity resulting from microplastic (MP) exposure has been extensively explored, particularly concerning the gut, liver, testis, and lung. However, under natural conditions, these effects are not restricted to specific organs or tissues. Investigating whether MP exposure presents a systemic threat to an entire organism, impacting factors such as lifespan, sleep, and fecundity, is essential. In this study, we investigated the effects of dietary exposure to two different doses of MPs (1-5 μm) using the terrestrial model organism <i>Drosophila melanogaster</i>. Results indicated that the particles caused gut damage and remained within the digestive system. Continuous MP exposure significantly shortened the lifespan of adult flies. Even short-term exposure disrupted sleep patterns, increasing the length of daytime sleep episodes. Additionally, one week of MP exposure reduced ovary size, with a trend towards decreased egg-laying in mated females. Although MPs did not penetrate the brain or ovaries, transcriptome analysis revealed altered gene expression in these tissues. In the ovary, Gene Ontology (GO) analysis indicated genotoxic effects impacting inflammation, circadian regulation, and metabolic processes, with significant impacts on extracellular structure-related pathways. In the brain, GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism. Overall, this study provides compelling evidence of the systemic negative effects of MP exposure, highlighting the urgent need to address and mitigate environmental MP pollution.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer's disease mice. 旋转磁场可抑制 Aβ 蛋白聚集并缓解阿尔茨海默病小鼠的认知障碍。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.034
Ruo-Wen Guo, Wen-Jing Xie, Biao Yu, Chao Song, Xin-Miao Ji, Xin-Yu Wang, Mei Zhang, Xin Zhang
{"title":"Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer's disease mice.","authors":"Ruo-Wen Guo, Wen-Jing Xie, Biao Yu, Chao Song, Xin-Miao Ji, Xin-Yu Wang, Mei Zhang, Xin Zhang","doi":"10.24272/j.issn.2095-8137.2024.034","DOIUrl":"10.24272/j.issn.2095-8137.2024.034","url":null,"abstract":"<p><p>Amyloid beta (Aβ) monomers aggregate to form fibrils and amyloid plaques, which are critical mechanisms in the pathogenesis of Alzheimer's disease (AD). Given the important role of Aβ1-42 aggregation in plaque formation, leading to brain lesions and cognitive impairment, numerous studies have aimed to reduce Aβ aggregation and slow AD progression. The diphenylalanine (FF) sequence is critical for amyloid aggregation, and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic rings. In this study, we examined the effects of a moderate-intensity rotating magnetic field (RMF) on Aβ aggregation and AD pathogenesis. Results indicated that the RMF directly inhibited Aβ amyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells <i>in vitro</i>. Using the AD mouse model APP/PS1, RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments, including exploration and spatial and non-spatial memory abilities. Tissue examinations demonstrated that RMF reduced amyloid plaque accumulation, attenuated microglial activation, and reduced oxidative stress in the APP/PS1 mouse brain. These findings suggest that RMF holds considerable potential as a non-invasive, high-penetration physical approach for AD treatment.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitogenomic phylogeny, biogeography, and cryptic divergence of the genus Silurus (Siluriformes: Siluridae). 硅鱼属(Siluriformes: Siluridae)的基因组系统发育、生物地理学和隐性分化。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2023.311
Weitao Chen, Nicolas Hubert, Yuefei Li, Shuli Zhu, Jun Wang, Denggao Xiang, Shang Gao, Chunni Kou, Jilong Wang, Tai Wang, Zhiqiang Liang, Junjie Wu, Xinhui Li, Jie Li
{"title":"Mitogenomic phylogeny, biogeography, and cryptic divergence of the genus <i>Silurus</i> (Siluriformes: Siluridae).","authors":"Weitao Chen, Nicolas Hubert, Yuefei Li, Shuli Zhu, Jun Wang, Denggao Xiang, Shang Gao, Chunni Kou, Jilong Wang, Tai Wang, Zhiqiang Liang, Junjie Wu, Xinhui Li, Jie Li","doi":"10.24272/j.issn.2095-8137.2023.311","DOIUrl":"10.24272/j.issn.2095-8137.2023.311","url":null,"abstract":"<p><p>The genus <i>Silurus</i>, an important group of catfish, exhibits heterogeneous distribution in Eurasian freshwater systems. This group includes economically important and endangered species, thereby attracting considerable scientific interest. Despite this interest, the lack of a comprehensive phylogenetic framework impedes our understanding of the mechanisms underlying the extensive diversity found within this genus. Herein, we analyzed 89 newly sequenced and 20 previously published mitochondrial genomes (mitogenomes) from 13 morphological species to reconstruct the phylogenetic relationships, biogeographic history, and species diversity of <i>Silurus</i>. Our phylogenetic reconstructions identified eight clades, supported by both maximum-likelihood and Bayesian inference. Sequence-based species delimitation analyses yielded multiple molecular operational taxonomic units (MOTUs) in several taxa, including the <i>Silurus asotus</i> complex (four MOTUs) and <i>Silurus microdorsalis</i> (two MOTUs), suggesting that species diversity is underestimated in the genus. A reconstructed time-calibrated tree of <i>Silurus</i> species provided an age estimate of the most recent common ancestor of approximately 37.61 million years ago (Ma), with divergences among clades within the genus occurring between 11.56 Ma and 29.44 Ma, and divergences among MOTUs within species occurring between 3.71 Ma and 11.56 Ma. Biogeographic reconstructions suggested that the ancestral area for the genus likely encompassed China and the Korean Peninsula, with multiple inferred dispersal events to Europe and Central and Western Asia between 21.78 Ma and 26.67 Ma and to Japan between 2.51 Ma and 18.42 Ma. Key factors such as the Eocene-Oligocene extinction event, onset and intensification of the monsoon system, and glacial cycles associated with sea-level fluctuations have likely played significant roles in shaping the evolutionary history of the genus <i>Silurus</i>.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting synaptic pathology in Alzheimer's disease. 针对阿尔茨海默氏症的突触病理学。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.183
Jing Cao, Yun-Wu Zhang
{"title":"Targeting synaptic pathology in Alzheimer's disease.","authors":"Jing Cao, Yun-Wu Zhang","doi":"10.24272/j.issn.2095-8137.2024.183","DOIUrl":"10.24272/j.issn.2095-8137.2024.183","url":null,"abstract":"","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models. COVID-19 的免疫生物学:来自动物模型的机制和治疗见解。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.062
Hong-Yi Zheng, Tian-Zhang Song, Yong-Tang Zheng
{"title":"Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models.","authors":"Hong-Yi Zheng, Tian-Zhang Song, Yong-Tang Zheng","doi":"10.24272/j.issn.2095-8137.2024.062","DOIUrl":"10.24272/j.issn.2095-8137.2024.062","url":null,"abstract":"<p><p>The distribution of the immune system throughout the body complicates <i>in vitro</i> assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteins as nanomagnets and magnetoreceptors. 作为纳米磁体和磁感受器的蛋白质
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.175
P J Hore
{"title":"Proteins as nanomagnets and magnetoreceptors.","authors":"P J Hore","doi":"10.24272/j.issn.2095-8137.2024.175","DOIUrl":"10.24272/j.issn.2095-8137.2024.175","url":null,"abstract":"","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Skeletal phenotypes and molecular mechanisms in aging mice. 衰老小鼠的骨骼表型和分子机制。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2023.397
Qiao Guan, Yuan Zhang, Zhi-Kun Wang, Xiao-Hua Liu, Jun Zou, Ling-Li Zhang
{"title":"Skeletal phenotypes and molecular mechanisms in aging mice.","authors":"Qiao Guan, Yuan Zhang, Zhi-Kun Wang, Xiao-Hua Liu, Jun Zou, Ling-Li Zhang","doi":"10.24272/j.issn.2095-8137.2023.397","DOIUrl":"10.24272/j.issn.2095-8137.2023.397","url":null,"abstract":"<p><p>Aging is an inevitable physiological process, often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks. Research on skeletal diseases caused by aging in humans is challenging due to lengthy study durations, difficulties in sampling, regional variability, and substantial investment. Consequently, mice are preferred for such studies due to their similar motor system structure and function to humans, ease of handling and care, low cost, and short generation time. In this review, we present a comprehensive overview of the characteristics, limitations, applicability, bone phenotypes, and treatment methods in naturally aging mice and prematurely aging mouse models (including <i>SAMP6</i>, <i>POLG</i> mutant, <i>LMNA</i>, <i>SIRT6</i>, <i>ZMPSTE24</i>, <i>TFAM</i>, <i>ERCC1</i>, <i>WERNER</i>, and <i>KL/KL</i>-deficient mice). We also summarize the molecular mechanisms of these aging mouse models, including cellular DNA damage response, senescence-related secretory phenotype, telomere shortening, oxidative stress, bone marrow mesenchymal stem cell (BMSC) abnormalities, and mitochondrial dysfunction. Overall, this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation. SIL1通过调节淀粉样前体蛋白的加工和Aβ的生成,改善APP23/PS45小鼠的认知障碍。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2023.363
Qunxian Wang, Yanshuang Jiang, Zijun Meng, Xiangjun Dong, Dongjie Hu, Liangye Ji, Weihui Zhou, Weihong Song
{"title":"SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation.","authors":"Qunxian Wang, Yanshuang Jiang, Zijun Meng, Xiangjun Dong, Dongjie Hu, Liangye Ji, Weihui Zhou, Weihong Song","doi":"10.24272/j.issn.2095-8137.2023.363","DOIUrl":"10.24272/j.issn.2095-8137.2023.363","url":null,"abstract":"<p><p>SIL1, an endoplasmic reticulum (ER)-resident protein, is reported to play a protective role in Alzheimer's disease (AD). However, the effect of SIL1 on amyloid precursor protein (APP) processing remains unclear. In this study, the role of SIL1 in APP processing was explored both <i>in vitro</i> and <i>in vivo</i>. In the <i>in vitro</i> experiment, SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695. In the <i>in vivo</i> experiment, AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates. Western blotting (WB), immunohistochemistry, RNA sequencing (RNA-seq), and behavioral experiments were performed to evaluate the relevant parameters. Results indicated that SIL1 expression decreased in APP23/PS45 mice. Overexpression of SIL1 significantly decreased the protein levels of APP, presenilin-1 (PS1), and C-terminal fragments (CTFs) of APP <i>in vivo</i> and <i>in vitro</i>. Conversely, knockdown of SIL1 increased the protein levels of APP, β-site APP cleavage enzyme 1 (BACE1), PS1, and CTFs, as well as APP mRNA expression in 2EB2 cells. Furthermore, SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice. Importantly, Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice. These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection. 具有 CD163 点突变的转基因猪对 HP-PRRSV 感染具有抵抗力。
IF 4 1区 生物学
Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.090
Ying Liu, Lin Yang, Hong-Yong Xiang, Ming Niu, Jia-Cheng Deng, Xue-Yuan Li, Wen-Jie Hao, Hong-Sheng Ou-Yang, Tong-Yu Liu, Xiao-Chun Tang, Da-Xin Pang, Hong-Ming Yuan
{"title":"Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection.","authors":"Ying Liu, Lin Yang, Hong-Yong Xiang, Ming Niu, Jia-Cheng Deng, Xue-Yuan Li, Wen-Jie Hao, Hong-Sheng Ou-Yang, Tong-Yu Liu, Xiao-Chun Tang, Da-Xin Pang, Hong-Ming Yuan","doi":"10.24272/j.issn.2095-8137.2024.090","DOIUrl":"10.24272/j.issn.2095-8137.2024.090","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 <sup>CD163</sup> cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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