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Virologica Sinica 2024年第1期39卷 71-80页

作者： Mengmeng Cao Qiannan Jia Jinghua Li Lili Zhao Li zhu Yufan Zhang Shan Li Tao Deng National Institute of pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100730China CAS key laboratory of pathogen microbiology and immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China

The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century.In this study,we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients.Sequence comparison of the three main protein subunits(PB2,PB1,and PA)of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution(E206K)was responsible for the observed impaired replication phenotype.Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus’s pathogenicity in vivo.Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1–PA complex to the nucleus at high temperature(39.5℃).Hence,this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.

关键词： H1N1 Influenza A virus Polymerase acidic protein Point mutation Viral replication

Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine

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Signal Transduction and Targeted Therapy 2024年第1期9卷 47-50页

作者： Mengyu Guo Mingjing Cao Jiufeng Sun Ziwei Chen Xin Wang Lianpan Dai George F.Gao Yuliang Zhao Yaling Wang Chunying Chen CAS key laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijingChina Guangdong Provincial Institute of Public Health Guangdong Provincial Center for Disease Control and PreventionGuangzhouChina CAS key laboratory of pathogen microbiology and immunology Institute of MicrobiologyBeijingChina

Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).

关键词： manganese immunity protective

Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

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Virologica Sinica 2024年第1期39卷 31-43页

作者： Dongyan Zhang Xiulin Wu Xing Xue Wenshi Li Ping Zhou Zhao Lv Kexin Zhao Fan Zhu State key laboratory of Virology and Department of Medical microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Hubei Province key laboratory of Allergy&immunology Wuhan UniversityWuhan430071China

Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years ago.Among these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of schizophrenia.Additionally,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia.Here,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated pathways.Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal controls.Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia.Studies indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce ferroptosis.Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities.Moreover,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by ERVW-1.In conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

关键词： ERVW-1 Glutathione peroxidase 4(GPX4) Solute carrier family 3 member 2(SLC3A2) Ferroptosis Schizophrenia

The infection kinetics and transmission potential of two Guaico Culex viruses in Culex quinquefasciatus mosquitoes

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Virologica Sinica 2024年第2期39卷 228-234页

作者： Ru-Yi Chen Teng Zhao Jing-Jing Guo Feng Zhu Na-Na Zhang Xiao-Feng Li Hai-Tao Liu Fei Wang Yong-Qiang Deng Cheng-Feng Qin College of Bioscience and Bioengineering Jiangxi Agricultural UniversityNanchang330045China State key laboratory of pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMSBeijing100071China School of Life Sciences Southwest Forestry UniversityKunming650224China

Guaico Culex virus(GCXV)is a newly identified segmented Jingmenvirus from Culex spp.mosquitoes in Central and South America.The genome of GCXV is composed of four or five single-stranded positive RNA segments.However,the infection kinetics and transmission capability of GCXV in mosquitoes remain unknown.In this study,we used reverse genetics to rescue two GCXVs(4S and 5S)that contained four and five RNA segments,respectively,in C6/36 cells.Further in vitro characterization revealed that the two GCXVs exhibited comparable replication kinetics,protein expression and viral titers.Importantly,GCXV RNAs were detected in the bodies,salivary glands,midguts and ovaries of Culex quinquefasciatus at 4–10 days after oral infection.In addition,two GCXVs can colonize Cx.quinquefasciatus eggs,resulting in positive rates of 15%–35%for the second gonotrophic cycle.In conclusion,our results demonstrated that GCXVs with four or five RNA segments can be detected in Cx.quinquefasciatus eggs during the first and second gonotrophic cycles after oral infection.

关键词： Guaico Culex virus(GCXV) Jingmenvirus Culex quinquefasciatus Vertical transmission

Approach from the laboratory to the field: New strategies in the control of mosquito-borne infectious diseases

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Science China Life Sciences 2024年

作者： Ziqian Xu Lianpan Dai Jun Liu National key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID) National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention CAS key laboratory of pathogen microbiology and immunology Institute of Microbiology Chinese Academy of Sciences

Vector-borne viruses, transmitted among humans and animal hosts through bites of vectors such as mosquitoes and ticks,pose a great and ongoing threat to public health and biosafety (Yang et al., 2022).Among them, dengue virus-induced epidemics, have dramatically increased worldwide in recent decades. The report released by the World Health Organization (WHO) at the end of 2023 showed that dengue epidemic globally surged in2023, with the number of reported cases nearing a historical peak.

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Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 115-127页

作者： Yang Yi Wenzhe Li Kefang Liu Heng Xue Rong Yu Meng Zhang Yang-Oujie Bao Xinyuan Lai Jingjing Fan Yuxi Huang Jing Wang Xiaomeng Shi Junhua Li Hongping Wei Kuanhui Xiang Linjie Li Rong Zhang Xin Zhao Xue Qiao Hang Yang Min Ye State key laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing100191China Yunnan Baiyao International Medical Research Center Peking UniversityBeijing100191China CAS key laboratory of pathogen microbiology and immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China CAS key laboratory of Special pathogens and Biosafety Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China Department of microbiology and Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing100191China Hubei Jiangxia laboratory Wuhan430000China Shenzhen Children's Hospital ShenzhenGuangdong518036China

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

关键词： COVID-19 Inflammation Licorice-saponin A3 Receptor-binding domain(RBD) SARS-CoV-2

Selenium-oxidizing Agrobacterium sp.T3F4 decreases arsenic uptake by Brassica rapa L.under a native polluted soil

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Journal of Environmental Sciences 2024年第4期138卷 506-515页

作者： Lijin An Chunzhi Zhou Lipeng Zhao Ao Wei Yiting Wang Huimin Cui Shixue Zheng State key laboratory of Agricultural microbiology College of Life Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China

Toxic arsenic(As)and trace element selenium(Se)are transformed by microorganisms but their complex interactions in soil-plant systems have not been fully understood.An Asand Se-oxidizing bacterium,Agrobacterium sp.T3F4,was applied to a native seleniferous As-polluted soil to investigate As/Se uptake by the vegetable Brassica rapa L.and As-Se interaction as mediated by strain T3F4.The Se content in the aboveground plants was significantly enhanced by 34.1%,but the As content was significantly decreased by 20.5% in the T3F4-inoculated pot culture compared to the control(P<0.05).Similar result was shown in treatment with additional 5 mg/kg of Se(IV)in soil.In addition,the As contents in roots were significantly decreased by more than 35% under T3F4 or Se(IV)treatments(P<0.05).Analysis of As-Se-bacterium interaction in a soil simulation experiment showed that the bioavailability of Se significantly increased and As was immobilized with the addition of the T3F4strain(P<0.05).Furthermore,an As/Se co-exposure hydroponic experiment demonstrated that As uptake and accumulation in plants was reduced by increasing Se(IV)concentrations.The 50% growth inhibition concentration(IC50)values for As in plants were increased about one-fold and two-fold under co-exposure with 5 and 10μmol/L Se(IV),respectively.In conclusion,strain T3F4 improves Se uptake but decreases As uptake by plants via oxidation of As and Se,resulting in decrease of soil As bioavailability and As/Se competitive absorption by plants.This provides a potential bioremediation strategy for Se biofortification and As immobilization in As-polluted soil.

关键词： Selenium oxidation Selenium biofortification Arsenite-oxidizing bacteria Arsenic immobilization Brassica rapa L

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The multi-kingdom microbiome catalog of the chicken gastrointestinal tract

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Biosafety and Health 2024年第2期6卷 101-115页

作者： Yanan Wang Mengqi Qu Yuhai Bi William J.Liu Sufang Ma Bo Wan Yongfei Hu Baoli Zhu Gaiping Zhang George F.Gao International Joint Research Center of National Animal immunology College of Veterinary MedicineHenan Agricultural UniversityZhengzhou 450046China CAS key laboratory of pathogen microbiology and immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)Beijing 100101China Longhu laboratory Zhengzhou 450046China University of Chinese Academy of Sciences Beijing 100049China NHC key laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China State key laboratory of Animal Nutrition and Feeding College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China

Chicken is an important food animal worldwide and plays an important role in human life by providing meat and eggs.Despite recent significant advances in gut microbiome studies,a comprehensive study of chicken gut bacterial,archaeal,and viral genomes remains unavailable.In this study,we constructed a chicken multi-kingdom microbiome catalog(CMKMC),including 18,201 bacterial,225 archaeal,and 33,411 viral genomes,and annotated over 6,076,006 protein-coding genes by integrating 135 chicken gut metagenomes and publicly available metagenome-assembled genomes(MAGs)from ten countries.We found that 812 and 240 MAGs in our dataset were putative novel species and genera,respectively,far beyond what was previously reported.The newly unclassified MAGs were predominant in Phyla Firmicutes_A(n=263),followed by Firmicutes(n=126),Bacteroidota(n=121),and Proteobacteria(n=87).Most of the classified species-level viral oper-ational taxonomic units belong to Caudovirales.Approximately,63.24%of chicken gut viromes are predicted to infect two or more hosts,including complete circular viruses.Moreover,we found that diverse auxiliary metabolic genes and antibiotic resistance genes were carried by viruses.Together,our CMKMC provides the largest integrated MAGs and viral genomes from the chicken gut to date,functional insights into the chicken gastrointestinal tract microbiota,and paves the way for microbial interventions for better chicken health and productivity.

关键词： Chicken Microbiome Metagenome assembled genomes Archaeome Virome Antibiotic resistance gene

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Medical Journals in China: From Wuyi Huijiang to Chinese Medical Journal and hLife

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hLife

hLife 2024年第1期2卷 1-3页

作者： Qun Yan Yi Shi George Fu Gao Editorial Office of hLife Institute of MicrobiologyChinese Academy of SciencesBeijingChina CAS key laboratory of pathogen microbiology and immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina

As Professor Jiaxi Lu,the former president of the Chinese Academy of Sciences(CAS),said,“Academic journals are both the‘tail’and the‘head’of a dragon”[1].Professor Zuoyan Zhu,former editor-in-chief of both Science China and Science Bulletin,also once said,“Let Chinese scientific journals grow along with scientific research in China”[2].Academic journals are important carriers for the exchange and dissemination of innovation and achievement in science and are important gardens for the training of scientific talent;also,they play an important role in carrying out an evaluation of academic work.Medical journals are an important component of the academic journal sphere,not only because they account for onethird of academic journals but also because they are directly related to human health。

关键词： journal Medical editor

The human-derived novel gut commensal Luoshenia tenuis regulates body weight and food intake in mice

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Food Science and Human Wellness 2024年第2期13卷 830-841页

作者： Yu Jiang Mengxuan Du Lisheng Xie Minzhi Jiang Yaokun Zhang Mingxia Bi Chang Liu Hongwei Liu Shuangjiang Liu State key laboratory of Microbial Technology Shandong UniversityQingdao 266237China State key laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China College of Life Science Hebei UniversityBaoding 071000China State key laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

Many studies have revealed that gut microbes modulate host metabolism.In this study,we characterized the therapeutic effects of a novel gut commensal Luoshenia tenuis against host metabolic disorders.First,by in silico analysis,we demonstrated that the L.tenuis was prevalent in the gut microbiomes of healthy humans but were depleted specifically in obesity cohorts.Further in vitro cultivation revealed that L.tenuis produced short chain fatty acids that were verified to modulate host metabolism and some other volatile metabolites to benefit hosts by anti-inflammation and anti-tumor.Second,gavage of the L.tenuis significantly decreased the body weight gain and food intake of high-fat diet-feeding C57BL/6J mice,which was in parallel with the changed expression level of genes related to satiety and feeding behavior.We then performed the gavage trial using diet induced obese mice,and it revealed that the administration of L.tenuis alleviated significantly the abnormal glucose and lipid metabolisms and reduced the inflammatory response.In summary,this study revealed a previously-unknown human gut commensal microbe that benefited host metabolism,and set the stage for the development of novel next-generation probiotic applicable for treatment of obesity and related metabolic disorders.

关键词： Luoshenia tenuis Gut microbe Feeding behavior Obesity Next-generation probiotic

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