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Novel Primate Bocaparvovirus Species 3 Identified in Wild Macaca Mulatta in China

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Virologica Sinica 2020年第1期35卷 34-42页

作者： Yuanyun Ao Zhaojun Duan Chinese Center for Disease Control and Prevention National Institute for Viral Disease Control and PreventionBeijingChina

Primate bocaparvovirus(BOV) is a possible cause of respiratory disorders and gastroenteritis in humans. However, the diversity and evolution of these viruses remain largely unknown, despite the identification of a growing number of BOVs in non-human primates(NHPs). Here, we report the identification of a novel BOV(provisionally named Macaca mulatta bocaparvovirus [MmBOV]) in the feces of wild Macaca mulatta in China by viral metagenomic analysis. Seven of 400 fecal samples from Macaca mulatta were positive for MmBOV. An almost complete genome sequence of 4,831 nucleotides was obtained, which had genomic organization and protein motifs similar to human bocaviruses(HOBVs), and shared characteristically low G/C content and weak codon usage bias. Sequence analyses of NS1, NP1, and VP1 revealed that Mm BOV was most closely related to HBOV4 of Primate bocaparvovirus 2(approximately 68.4%/70.6%, 73.3%/67.6%, and 70.4%/73.1% nucleotide/amino acid identities, respectively). Additionally, phylogenetic analysis revealed that Mm BOV formed an independent peripheral branch, but clustered closely with those of the Primate bocaparvovirus species in the BOV genus(particularly HBOV4). These data strongly suggest that HBOV4 originated from NHP bocaparvoviruses around 200–300 years ago, and that NHPs may act as HBOV reservoirs. Following the International Committee of Taxonomy for Viruses guidelines, we propose Mm BOV as a new species(tentatively named Primate bocaparvovirus 3) in the genus Bocaparvovirus, which is the first report of a novel species of primate BOV. Our data facilitate future research on the genetic diversity and evolution of primate bocaparvoviruses and highlight the importance of bocaparvovirus surveys in wild NHPs.

关键词： Primate bocaparvovirus(BOV) Novel species Macaca mulatta Sequence analysis Phylogenetic analysis

IGF2BP3 Enhances the Growth of Hepatocellular Carcinoma Tumors by Regulating the Properties of Macrophages and CD8^(+)T Cells in the Tumor Microenvironment

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Journal of Clinical and Translational Hepatology 2023年第6期11卷 1308-1320页

作者： Lingyu Ma Jiayu Jiang Qin Si Chong Chen Zhaojun Duan Department of Immunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijingChina

Background and Aims:Overexpression of IGF2BP3 is associated with the prognosis of hepatocellular carcinoma(HCC).However,its role in regulating tumor immune microenvironment(TME)is not well characterized.Here,we investigated the effects of IGF2BP3 on macrophages and CD8^(+)T cells within the TME of HCC.Methods:The relationship between IGF2BP3 and immune cell infiltration was analyzed using online bioinformatics tools.Knockout of IGF2BP3 in mouse hepatoma cell line Hepa1-6 was established using CRISPR/Cas9 technology.In vitro cell coculture and subcutaneously implanted hepatoma mice model were used to explore the effects of IGF2BP3 on immune cells.Expression of CCL50l transforming growth factor beta 1(TGF-β1)was detected with quantitative real-time polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay.The binding of IGF2BP3 and its target RNA was verified by trimolecular fluorescence complementation system and RNA immunoprecipitation followed by quantitative or semiquantitative polymerase chain reaction.Results:IGF2BP3 expression was elevated in HCC and was positively correlated with macrophage infiltration.Patients with higher IGF2BP3 expression and lower macrophage infiltration had a better survival rate.We found that IGF2BP3 could bind to the mRNA of CCL5 or TGF-β1,increasing their expression,and inducing macrophage infiltration and M2 polarization while inhibiting the activation of CD8^(+)T cells.Furthermore,inhibition of IGF2BP3 combined with anti-CD47 antibody treatment significantly suppressed the growth of hepatoma in Hepa1-6 xenograft tu-mor mice.Conclusions:IGF2BP3 promoted the infiltration and M2-polarization of macrophages and suppressed CD8^(+)T activation by enhancing CCL5 and TGF-β1 expression,which facilitated the progression of Hepa1-6 xenograft tumor.

关键词： Hepatocellular carcinoma IGF2BP3 TGF-β1 CCL5 M2 macrophage CD8^(+)T cell

MOPCS: next-generation nucleic acid molecular biosensor

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National Science Review 2022年第9期9卷 139-141页

作者： Quan Liu Shang Chen Li Wang Zhaojun Duan Fuquan Xie Guojun Zhao Yunde Hou Dixian Luo Laboratory Medicine Center Huazhong University of Science and Technology Union Shenzhen Hospital(Nanshan Hospital) Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging School of Biomedical Engineering Shenzhen University Health Science Center National Institute for Viral Disease Control and Prevention China Center for Disease Control and Prevention Department of Laboratory Medicine Shenzhen Children's Hospital The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan City People's Hospital

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a huge impact on the world, causing millions of deaths and a serious blow to the global economy. SARS-CoV-2 can aack most body tissues with devastating consequences [1].e current global SARS-CoV-2 outbreak has exposed our shortcomings in the prevention and control of infectious diseases,

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Molecular Epidemiological Characteristics of Gastroenteritis Outbreaks Caused by Norovirus GII.4 Sydney[P31]Strains—China,October 2016–December 2020

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China CDC weekly 2021年第53期3卷 1127-1132,I0001页

作者： Xi Zhu Yaqing He Xingyan Wei Xiangyu Kong Qing Zhang Jingxin Li Miao Jin Zhaojun Duan Key Laboratory of Medical Virology and Viral Diseases Ministry of Health of the People’s Republic of ChinaBeijingChinaNational Institute for Viral Disease Control and PreventionChina CDCBeijingChina Shenzhen Center for Disease Control and Prevention ShenzhenGuangdongChina.

Introduction:Human noroviruses are the leading cause of acute viral gastroenteritis(AGE)worldwide in all age groups.GII.4 strains have been the predominant genotype circulating globally over the last 2 decades and since 2012.GII.4 Sydney viruses have emerged and caused the majority of AGE outbreaks worldwide.Methods:Data from norovirus outbreaks from the laboratory-based surveillance of norovirus outbreaks in China(CaliciNet China)between October 2016–December 2020 were analyzed.Results:During October 2016–December 2020,1,954 norovirus outbreaks were reported,and positive fecal samples from 1,352(69.19%)outbreaks were genotyped.GII.4 Sydney[P31]viruses accounted for 2.1%(October 2016–August 2017),5.5%(September 2017–August 2018),3.3%(September 2018–August 2018),26.6%(September 2019–August 2020),and and 1.1%(September 2020–December 2020)of GII outbreaks,respectively.Compared to reference strains of GII.4 Sydney[P31]from 2012 to 2013,7 amino acid mutations in epitopes[A(297,372 and 373),B(333),E(414),and H(309 and 310)]and 1 in human histo-blood group antigens binding site at site II 372 were found by analyzing 9 GII.4 Sydney[P31]complete genomic sequences.Conclusions:This report identified the genomic variation of GII.4 Sydney[P31]from CaliciNet China.Continued surveillance with prompt genotyping and genetic analysis is necessary to monitor the emergence of novel GII.4 variants.

关键词： Sydney GII prompt

The Functional Characterization of Bat and Human P[3] Rotavirus VP8*s

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Virologica Sinica 2021年第5期36卷 1187-1196页

作者： Dandi Li Mengxuan Wang Tongyao Mao Mingwen Wang Qing Zhang Hong Wang Lili Pang Xiaoman Sun Zhaojun Duan National Health Commission Key Laboratory for Medical Virology and Viral Diseases Beijing 102206China National Institute for Viral Disease Control and Prevention China CDCBeijing 102206China

P[3]rotavirus(RV)has been identified in many species,including human,simian,dog,and bat.Several glycans,including sialic acid,histo-blood group antigens(HBGAs)are reported as RV attachment factors.The glycan binding specificity of different P[3]RV VP8*s were investigated in this study.Human HCR3 A and dog P[3]RV VP8*s recognized glycans with terminal sialic acid and hemagglutinated the red blood cells,while bat P[3]VP8*showed neither binding to glycans nor hemagglutination.However,the bat P[3]VP8*mutant of C189 Y obtained the ability to hemagglutinate the red blood cells,while human P[3]HCR3 A/M2-102 mutants of Y189 C lost the ability.Sequence alignment and structural analysis indicated that residue 189 played an important role in the ligand recognition and may contribute to the cross-species transmission.Structural superimposition exhibited that bat P[3]VP8*model was quite different from the simian P[3]Rhesus rotavirus(RRV)P[3]VP8*,indicating that bat P[3]RV was relatively distinct and partially contributed to the no binding to tested glycans.These results promote our understanding of P[3]VP8*/glycans interactions and the potential transmission of bat/human P[3]RVs,offering more insight into the RV infection and prevalence.

关键词： Bat rotavirus PVP8* Glycan binding specificity Hemagglutination Sialic acid

Targeting carnitine palmitoyl transferase 1A(CPT1A)induces ferroptosis and synergizes with immunotherapy in lungg cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1675-1689页

作者： Lei Ma Chong Chen Chunxing Zhao Tong Li Lingyu Ma Jiayu Jiang Zhaojun Duan Qin Si Sung-Hsien Chuang Rong Xiang Yunping Luo Department of mmunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBejing 100005China Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Department of Lung Cancer Surgery Tianjin Medical University General HospitalTianjin 300052China Immunology Research Center National Health Research InstitutesZhunanMiaoliTaiwanROC Department of Immunology Nankai UniversityTianjin 300071China

Despite the successful application of immune checkpoint therapy,no response or recurrence is typical in lung cancer.Cancer stem cells(CSCs)have been identified as a crucial player in immunotherapy-related resistance.Ferroptosis,a form of cell death driven by iron-dependent lipid peroxidation,is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with immunotherapy.Metabolic adaption of CsCs drives tumor resistance,yet the mechanisms of their ferroptosis defense in tumor immune evasion remain elusive.Here,through metabolomics,transcriptomics,a lung epithelialspecific Cptla-knockout mouse model,and clinical analysis,we demonstrate that CPT1A,a key rate-limiting enzyme of fatty acid oxidation,acts with L-carnitine,derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8^(+)T cells inactivation in lung cancer.Mechanistically,CPT1A restrains ubiquitination and degradation of c-Myc,while c-Myc transcriptionally activates CPT1A expression.The CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating,thereby suppressing ferroptosis in CSCs.Significantly,targeting CPT1A enhances immune checkpoint blockadeinduced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice.The results illustrate the potential of a mechanismguided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CsCs to improve the efficacy of lung cancer immunotherapy.

关键词： immunotherapy metabolism peroxidation

Two novel bocaparvovirus species identified in wild Himalayan marmots

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Science China(Life Sciences) 2017年第12期60卷 1348-1356页

作者： Yuanyun Ao Xiaoyue Li Lili Li Xiaolu Xie Dong Jin Jiemei Yu Shan Lu Zhaojun Duan National Institute for Viral Diseases Control and Prevention Chinese Center for Disease Control and PreventionBeijing 100052China Laboratory Department the First People's Hospital of AnqingAnqing 246000China Peking Union Medical College Hospital Beijing 100730China National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China

Bocaparvovirus(BOV) is a genetically diverse group of DNA viruses and a possible cause of respiratory, enteric, and neurological diseases in humans and animals. Here, two highly divergent BOVs(tentatively named as Himalayan marmot BOV,HMBOV1 and HMBOV2) were identified in the livers and feces of wild Himalayan marmots in China, by viral metagenomic analysis. Five of 300 liver samples from Himalayan marmots were positive for HMBOV1 and five of 99 fecal samples from these animals for HMBOV2. Their nearly complete genome sequences are 4,672 and 4,887 nucleotides long, respectively, with a standard genomic organization and containing protein-coding motifs typical for BOVs. Based on their NS1, NP1, and VP1,HMBOV1 and HMBOV2 are most closely related to porcine BOV SX/1-2(approximately 77.0%/50.0%, 50.0%/53.0%, and79.0%/54.0% amino acid identity, respectively). Phylogenetic analysis of these three proteins showed that HMBOV1 and HMBOV2 formed two distinctly independent branches in BOVs. According to these results, HMBOV1 and HMBOV2 are two different novel species in the Bocaparvovirus genus. Their identification expands our knowledge of the genetic diversity and evolution of BOVs. Further studies are needed to investigate their potential pathogenicity and their impact on Himalayan marmots and humans.

关键词： emerging infectious diseases bocaparvovirus novel Himalayan marmot

Higher levels of circulating monocyte-platelet aggregates are correlated with viremia and increased sCD 163 levels in HIV- 1 infection

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Cellular & Molecular Immunology 2015年第4期12卷 435-443页

作者： Hua Liang Zhaojun Duan Dan Li Dongliang Li ZhengWang Li Ren Tao Shen Yiming Shao State Key Laboratory for Infectious Disease Prevention and Control National Center for AIDS/STD Control and Prevention China CDC CollaborativeInnovation Center for Diagnosis and Treatment of Infectious Diseases Beijing China Department of Microbiology School of Basic Medical SciencesPekin8 University Beijing China and 3Beijing Chaoyang District Center for Disease Control and Prevention Beijing China Correspondence: Dr T Shen Department of Microbiology Peking University Health Science Center Beijing 100191 China.

Increased levels of monocyte-platelet aggregates （MPAs） are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-l-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 （PSGL-1） was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-I.

关键词： HIV-1 immune activation monocytes platelets sCD163

Genetic Analysis of an Emerging GII.P2–GII.2 Norovirus Associated with a 2016 Outbreak of Acute Gastroenteritis in China

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Virologica Sinica 2019年第1期34卷 111-114页

作者： Yuanyun Ao Xiaolu Xie Xiaogen Dong Miao Jin Zhaojun Duan National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention Graduate School Peking Union Medical College Fengtai District Center for Disease Control and Prevention

Dear Editor,Noroviruses are positive-sense, single-stranded RNA viruses belonging to Caliciviridae and account for more than 50%of all acute gastroenteritis (AGE) outbreaks worldwide and cause an estimated 200,000 deaths per year among children\5 years of age, primarily in developing countries (Hall et al. 2012;Glass et al. 2009). The norovirus genome contains three open reading frames (ORFs).

关键词： GII.2 Norovirus Associated with a 2016 Outbreak of Acute Gastroenteritis in China Genetic Analysis of an Emerging GII.P2