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Hsp90βis critical for the infection of severe fever with thrombocytopenia syndrome virus

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Virologica Sinica 2024年第1期39卷 113-122页

作者： Bo Wang Leike Zhang Fei Deng Zhihong Hu Manli Wang Jia Liu State Key Laboratory of virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China The Third Affiliated Hospital of Guangzhou Medical University Guangzhou Medical UniversityGuangzhou511436China

Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown.The heat-shock protein 90(Hsp90)family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses.Here,we showed that Hsp90 is an important host factor involved in SFTSV infection.Hsp90 inhibitors significantly reduced SFTSV replication,viral protein expression,and the formation of inclusion bodies consisting of nonstructural proteins(NSs).Among viral proteins,NSs appeared to be the most reduced when Hsp90 inhibitors were used,and further analysis showed that their translation was affected.Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with them.Knockdown of Hsp90βexpression also inhibited replication of SFTSV.These results suggest that Hsp90βplays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.

关键词： Severe fever with thrombocytopenia syndrome virus(SFTSV) Heat-shock protein 90 Hsp90β Host-virus interaction Nonstructural protein

Respiratory Viruses and Mycoplasma Pneumoniae Surveillance Among Hospitalized Children with Acute Respiratory Infections—Wuhan City,Hubei Province,China,September-November 2023

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China CDC weekly 2024年第8期6卷 139-142页

作者： Ying Li Yi Yan Jiaming Huang Yue Shi Hui Du Chao Xiong Kai Chen Di Liu Xiaoxia Lu Computational virology group Center for Bacteria and Viruses Resources and BioinformationWuhan Institute of VirologyChinese Academy of SciencesWuhan CityHubei ProvinceChina Department of Respiratory Medicine Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina Pediatric Respiratory Disease Laboratory Institute of Maternal and Child HealthWuhan Children's HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina University of Chinese Academy of Sciences BeijingChina CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan CityHubei ProvinceChina Data Center Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina

Summary What is already known about this topic?Acute respiratory infections(ARIs)are a significant contributor to illness and death in children.There has been a notable rise in the occurrence of ARIs and the associated pathogens in China,which has garnered worldwide attention.What is added by this report?This study conducted a retrospective analysis of the clinical characteristics of children with ARIs in Wuhan City from September to November 2023.

关键词： November Wuhan Hubei

AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy

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Chinese Medical Journal 2024年第2期137卷 222-231页

作者： Yichun Yin Jian Wang Junxuan Yi Kaiyue Zhang Zimeng Yin Shunzi Jin Baisong Zheng Public Health of College Jilin UniversityJilinChangchun 130021China Institute of virology and AIDS Research The First Hospital of Jilin UniversityJilinChangchun 130021China NHC Key Laboratory of Radiobiology(Jilin University) JilinChangchun 130021China

Background:Radiation(IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment(TME).Wee1,a cell cycle regulator,can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1(CDK1).Meanwhile,programed death-1/programed death ligand-1(PD-1/PDL-1)blockade is closely related to TME.This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody(anti-PD-1 Ab)on radiosensitization of hepatoma.Methods:The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide(MTT)assay on human and mouse hepatoma cells HepG2,Hepa1-6,and H22.The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro.A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice,which were divided into control group,IR group,AZD1775 group,IR+AZD1775 group,IR+anti-PD-1 Ab group,and the IR+AZD1775+anti-PD-1 Ab group.Cytotoxic CD8^(+)T cells in TME were analyzed by flow cytometry.Results:Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro.AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage.AZD1775 treatment also reduced the proportion of PD-1^(+)/CD8^(+)T cells in the spleen of hepatoma subcutaneous xenograft mice.Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferonγ(IFNγ)^(+)or Ki67^(+)CD8 T cells and decreasing the levels of CD8^(+)Tregs cells in the tumor and spleen of the hepatoma mice model,indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγexpression,enhancing CD8^(+)T cells proliferation,and weakening CD8^(+)T cells depletion.Conclusions:This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improv

关键词： Hepatoma Radiation AZD1775 Anti-PD-1 antibody DNA damage Tumor microenvironment

C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus

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Virologica Sinica 2024年第2期39卷 277-289页

作者： Lei Yu Xinjin Liu Xiaoqin Wei Junrui Ren Xueyun Wang Shuwen Wu Ke Lan State Key Laboratory of virology Medical Research InstituteCollege of Life SciencesWuhan UniversityWuhan430072China Frontier Science Center for Immunology and Metabolism Wuhan UniversityWuhan430072China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan430072China

Influenza A virus(IAV)binds sialic acid receptors on the cell surface to enter the host cells,which is the key step in initiating infection,transmission and pathogenesis.Understanding the factors that contribute to the highly efficient entry of IAV into human cells will help elucidate the mechanism of viral entry and pathogenicity,and provide new targets for intervention.In the present study,we reported a novel membrane protein,C1QTNF5,which binds to the hemagglutinin protein of IAV and promotes IAV infection in vitro and in vivo.We found that the HA1 region of IAV hemagglutinin is critical for the interaction with C1QTNF5 protein,and C1QTNF5 interacts with hemagglutinin mainly through its N-terminus(1–103 aa).In addition,we further demonstrated that overexpression of C1QTNF5 promotes IAV entry,while blocking the interaction between C1QTNF5 and IAV hemagglutinin greatly inhibits viral entry.However,C1QTNF5 does not function as a receptor to mediate IAV infection in sialic acid-deficient CHO-Lec2 cells,but promotes IAV to attach to these cells,suggesting that C1QTNF5 is an important attachment factor for IAV.This work reveals C1QTNF5 as a novel IAV attachment factor and provides a new perspective for antiviral strategies.

关键词： C1QTNF5 Influenza A virus Viral entry Hemagglutinin Attachment factor

The immune response to SARS-CoV-2 in people with HIV

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Cellular & Molecular Immunology 2024年第2期21卷 184-196页

作者： Maxine A.Höft Wendy A.Burgers Catherine Riou Institute of Infectious Disease and Molecular Medicine University of Cape TownCape TownSouth Africa Division of Medical virology Department of PathologyUniversity of Cape TownCape TownSouth Africa Wellcome Centre for Infectious Diseases Research in Africa University of Cape TownCape TownSouth Africa

This review examines the intersection of the HIV and SARS-CoV-2 pandemics.People with HIV(PWH)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral control.While COVID-19 in those with wellcontrolled HIV infection poses no greater risk than that for HIV-uninfected individuals,people with advanced HIV disease are more vulnerable to poor COVID-19 outcomes.COVID-19 vaccines are effective and well tolerated in the majority of PWH,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in PWH.This is likely a result of suboptimal humoral and cellular immune responses after vaccination.People with advanced HIV may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent infection.COVID-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely immunocompromised.We recommend continued research and monitoring of PWH with SARS-CoV-2 infection,especially in areas with a high HIV burden.

关键词： SARS-CoV-2 HIV Immune dysfunction Vaccine efficacy Prolonged infection Immunogenicity

Resurgence of measles virus infection in an eliminated country, Sri Lanka

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Asian Pacific Journal of Tropical Medicine 2024年第5期17卷 208-213页

作者： Merennage Anusha Yasanthi Fernando Gankandage Prabhath Chathuranga Kaanthaka Gunaradha Abeygunasekara Dedunu Dias Weligamage Janaki Indira Abeynayake Department of Medical Microbiology and Immunology Faculty of MedicineUniversity of ColomboSri Lanka Department of virology Medical Research InstituteColombo 08Sri Lanka Department of Medical Administration Medical Research InstituteColombo 08Sri Lanka

Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the outbreak.Methods:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri Lanka.According to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,respectively.Selected RNA positive samples were sequenced at reference laboratory,India.Analysis of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella Laboratory.Data was analyzed using descriptive statistics.Results:Of the total 1132 serum samples and 497 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(49.5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or both.Males(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive patients.All provinces reported measles positive cases.All samples sequenced(100%,n=42)were genotype D8 with 95.2%(n=40)bearing Victoria.Australia origin.Conclusions:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating globally.Further,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.

关键词： Measles elimination Resurgence of measles Sri Lanka Genotype D8 National Measles Rubella Laboratory

Comparison of the early curative effect in patients undergoing mechanical vs. bioprosthetic aortic valve replacement with concomitant annuloplasty by the Nicks procedure

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South China Journal of Cardiology 2024年第1期25卷 29-37页

作者：吴浩向鸿谟王露朱平 Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510100China Guangdong Provincial Key Laboratory of pathogenesis Targeted Prevention and Treatment of Heart DiseaseGuangzhou Key Laboratory of Cardiac Pathogenesis and PreventionGuangzhouGuangdong 510100China

Background The probability of prosthesis-patient mismatch(PPM)is high in aortic valve replacement surgery for small aortic valve annulus,which increases the postoperative prosthetic valve transvalvular pressure gradient.Concurrent aortic annuloplasty is a commonly applied surgical procedure,but there is currently no uniform standard or guideline on the type of prosthetic valve that should be used during surgery.Therefore,this study aimed to analyze whether there was any difference in the short-term prognosis between the choice of mechanical valves and bioprosthetic valves during aortic valve replacement surgery with concomitant aortic annuloplasty by the Nicks procedure.Methods A retrospective analysis was conducted based on the clinical data from 55 patients undergoing aortic valve replacement surgery with concomitant annuloplasty by the Nicks procedure at the Cardiac Surgery Department of Guangdong Provincial People’s Hospital from November 2021 to December 2023.In this study,all patients received aortic annuloplasty by the Nicks procedure.Among these patients,30 were in the mechanical valve group,while the other 25 were in the bioprosthetic valve group.Data including left ventricular end-diastolic/endsystolic diameters,left ventricular ejection fraction,interventricular septal thickness,left ventricular posterior wall thickness,transvalvular pressure gradient,left ventricular fractional shortening,and left ventricular mass index were collected 1 week preoperatively and 1 week and 3 months postoperatively.Information on gender,age,body surface area,types of perioperative complications,operation time,complication rates,and outcomes was also collected.Results Among the 55 patients enrolled in this study,4 died.The main causes of death included postoperative low cardiac output syndrome,severe pulmonary infection,and multi-organ dysfunction.Meanwhile,there was a statistically significant difference in left ventricular end-diastolic diameter between the mechanical valve group and the biological valve group 1 week af

关键词： Valve replacement Small aortic annulus Nicks procedure Prosthesis-patient mismatch Mechani-cal valve Bioprosthetic valve

More common RNAemia in the early stage of severe SARS-CoV-2 BF.7.14 infections in pediatric patients

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Biosafety and Health 2024年第1期6卷 5-11页

作者： Yu Sun Runan Zhu Yang Pan Ri De Shuang Liu Liping Jia Bing Lv Xiaoyun Li Dongmei Chen Yao Yao Dong Qu Daitao Zhang Linqing Zhao Laboratory of virology Bejing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBejing 100020China Institute for Infectious Disease and Endemic Disease Control Bejing Center for Disease Control and Prevention Beijing 100013China Department of Intensive Care Unit Affiliated Children's Hospital of Capital Institute of PediatricsBeijing 100020China

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)outbreak in Beijing remain elusive.SARS‐CoV‐2‐positive children admitted to the intensive care unit(ICU)with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis‐based multiplex PCR from December 12,2022,to January 24,2023.The SARS‐CoV‐2 subvariants were identified using next‐generation sequencing.Plasma was positive for two(positive;P),one(suspicious;S),or no(negative;N)SARS‐CoV‐2 genes were classified as plasmatic RNA‐positive(RNAemia;P+S)or without RNAemia(N).Clinical and laboratory data of the enrolled cases were then collected and analyzed.The 34 enrolled children included 26 males and 24 younger than three years.All were negative for other respiratory pathogens.BF.7.14(18/29)was the predominant subvariant.Viral loads in respiratory specimens,hours from symptom onset to the first respiratory specimen collection(time‐variable),with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs.N and RNAemia vs.without RNAemia group.Among most cases,the T lymphocyte ratios decreased,while the cytokine level and the B lymphocyte ratio increased.The time variables were 2.22±2.05 and 4.00±2.49 days in BF.7.14 and BA.5.2 infections,respectively.In conclusion,SARS‐CoV‐2 was more likely to cause severe infections among males aged≤3 years old with comorbidities during the SARS‐CoV‐2 outbreak in Beijing,while RNAemia is more common in children at the early stage of severe BF.7.14 infections,and most had high cytokine levels and B‐cell activation.

关键词： Severe SARS‐CoV‐2 infection Pediatric patients Risk factor RNAemia BF.7.14

Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2