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Cellular Caspase-3 Contributes to EV-A71 2Apro-Mediated Down-Regulation of IFNAR1 at the Translation Level

Virologica Sinica 2020年第1期35卷 64-72页

作者： Bangtao Chen Yuya Wang Xinyi Pei Sanyuan Wang Hao Zhang Yihong Peng department of microbiology&infectious disease center School of Basic Medical SciencesPeking University Health Science CenterBeijing 100083China

Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a.

关键词： Enterovirus A71(EV-A71) Interferon alpha receptor 1(IFNAR1) 2A protease(2Apro) Caspase-3 Eukaryotic initiation factor 4GI(eIF4GI)

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World Journal of Clinical Cases 2025年第6期13卷 24-29页

作者： Wen-Jin Yuan Yi-Juan Zheng Bing-Rong Zhang Yi-Jie Lin You Li Yan-Yan Qiu Xue-Ping Yu department of Infection disease Clinical Medical Research Center for Bacterial and Fungal Infectious Diseases of Fujian provinceFujian Medical University Affiliated First Quanzhou HospitalQuanzhou 362000Fujian ProvinceChina

BACKGROUND Hydroxyurea,an antimetabolite,is frequently prescribed for various hemato-logical disorders,and its common side effects include gastrointestinal problems,cutaneous or mucosal lesions and pyrexia/*** SUMMARY This study reports the case of a 67-year-old woman who developed recurrent abdominal pain after 10 years of continuous hydroxyurea therapy for primary *** revealed an ileocecal *** discontinuing hydroxyurea therapy for 6 months,follow-up colonoscopy showed a significant reduction in the *** We consider cecal ulcers as a rare complication of hydroxyurea therapy which typically resolves upon stopping the drug.

关键词： Hydroxyurea Ulcer Abdominal pain Thrombocythemia Colonoscopy Case report

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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 2025年第01期 303-305页

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 PreventionChinese Center for Disease Control and Prevention CAS Key Laboratory of Pathogen microbiology and Immunology Institute of MicrobiologyChinese 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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Vaginal Delivery and Breastfeeding Benefit Infant Immune Response to Hepatitis B Vaccine:A Prospective Cohort Study

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 899-907页

作者： Huiqing Liu Lili Li Yali Li Minmin Liu Yarong Song Feng Ding Xiaoshu Zhang Jie Li Jinchang Municipal center for disease Control and Prevention JinchangGansuChina department of microbiology&infectious disease center School of Basic Medical SciencesPeking University Health Science CenterBeijingChina Gansu Provincial center for disease Control and Prevention LanzhouGansuChina

Background and Aims:Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants,and the immune response of infants to vaccines is closely related to their immune *** large prospective cohort study aimed to explore the effects of delivery and feeding mode on infant’s immune response to hepatitis B vaccine(HepB).Methods:A total of 1,254 infants who completed the whole course of HepB immunization and whose parents were both HBsAg negative were enrolled from infants born in Jinchang City during 2018-2019 by cluster sampling ***:Twenty(1.59%)of the 1,254 infants were nonresponders to *** the other 1,234 infants,10.05%(124/1,234),81.69%(1,008/1,234)and 8.27%(102/1,234)of infants had low,medium,and high responses to HepB,*** regression analysis showed that cesarean section(OR:8.58,95%CI:3.11-23.65,p<0.001)and birth weight<3.18 kg(OR:5.58,95%CI:1.89-16.51,p=0.002)were independent risk factors for infant nonresponse to HepB,and cesarean section(OR:7.63,95%CI:4.64-12.56,p<0.001),formula feeding(OR:4.91,95%CI:1.47-16.45,p=0.001),maternal antiHBs negativity(OR:27.2,95%CI:10.67-69.35,p<0.001),paternal non-response history of HepB(OR:7.86,95%CI:2.22-27.82,p=0.014)and birth weight<3.22 kg(OR:4.00,95%CI:2.43-6.59,p<0.001)were independent risk factors for infant low response to *** cases where birth weight and genetic factors are unmodifiable and maternal anti-HBs effects are controversial,it makes sense to enhance infant response by changing delivery and feeding ***:Natural vaginal delivery and breastfeeding are beneficial to the infant’s immune response to HepB.

关键词： Hepatitis B vaccine Immune response Anti-HBs Vaginal delivery Breastfeeding

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The frst avian infuenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report

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Frontiers of Medicine 2013年第3期7卷 333-344页

作者： Enfu Chen Fenjuan Wang Huakun Lv Yanjun Zhang Hua Ding Shelan Liu Jian Cai Li Xie Xiaoping Xu Chengliang Chai Haiyan Mao Jimin Sun Junfen Lin Zhao Yu Lianhong Li Zhiping Chen Shichang Xia department of infectious diseases Zhejiang Center for Disease Control and Prevention department of infectious diseases Xiaoshan District Center for Disease Control and Prevention department of infectious diseases Hangzhou Center for Disease Control and Prevention department of infectious diseases Jiande Center for Disease Control and Prevention

This study reports the frst death caused by a novel avian infuenza A(H7N9)virus in Zhejiang Province,*** patient had chronic hepatitis B and history of exposure to *** patient initially complained of diarrhea and infuenza-like symptoms on March 7 and 14 *** disease progressed to severe pneumonia,sustained hypoxia,and coagulation *** patient died on March 27 because of respiratory failure,multiple organ failure,and disseminated intravascular coagulation without oseltamivir *** H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai,Jiangsu,Anhui,*** of hemagglutinin,neuramidinase,and matrix genes indicated that the isolates share the same avian origin,have low virulence,and are sensitive to oseltamivir,but are resistant to *** the isolate that caused the fatality exhibited substitution of Q226I in the HA gene,which indicates a potentially enhanced human *** secondary transmission rate was 1.6%(2/125).Only two health workers presented with infuenza-like symptoms,and they subsequently tested negative for H7N9 *** conclusion,underlying disease,late diagnosis,and untimely antiviral treatment are possible high-risk factors for infections and death caused by the lowpathogenicity avian infuenza A(H7N9).Person-to-person transmission of the H7N9 virus was not detected among close contacts,but such transmission should be investigated in the *** and enhancing surveillance will help in the early discovery and diagnosis of suspected cases,which will reduce the number of severe cases and deaths.

关键词： avian influenza A (H7N9) virus epidemiology contacts person-to-person transmission

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Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第13期21卷 3860-3866页

作者： Shan-Long Ding Zi-Wei Yang Jie Wang Xiao-Lei Zhang Xiang-Mei Chen Feng-Min Lu department of microbiology and infectious disease center School of Basic Medical SciencesPeking University Health Science Center

Chronic hepatitis B virus(HBV) infection is a critical risk factor for the carcinogenesis and progression of hepatocellular carcinoma(HCC). It promotes HCC development by inducing liver fibrogenesis, genetic and epigenetic alterations, and the expression of active viral-coded proteins. Effective antiviral treatments inhibit the replication of HBV, reduce serum viral load and accelerate hepatitis B e antigen serum conversion. Timely initiation of antiviral treatment is not only essential for preventing the incidence of HCC in chronic hepatitis B patients, but also important for reducing HBV reactivation, improving liver function, reducing or delaying HCC recurrence, and prolonging overall survival of HBV-related HCC patients after curative and palliative therapies. The selection of antiviral drugs, monitoring of indicators such as HBV DNA and hepatitis B surface antigen, and timely rescue treatment when necessary, are essential in antiviral therapies for HBVrelated HCC.

关键词： Chronic hepatitis B Hepatocellular carcinoma Antiv

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GRK6 expression in patients with hepatocellular carcinoma

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Asian Pacific Journal of Tropical Medicine 2013年第3期6卷 220-223页

作者： Ya-Ping Li department of infectious disease Huanggang Center Hospital

Objective:To investigate the expression and potential roles of G protein—coupled receptor kinase 6[GRK6]in hepatocellular carcinoma(HCC) ***:Immunohistochemistry and Western blot was performed to determine GRK6 expression in 73 HCC *** the correlation with clinieopathological features was also ***:GKK6 expression was significantly higher in HCC than that in normal hepatic ***6 was positively correlated with proliferation marker Ki-67,clinical stage,metastasis and survival ***: Our results suggested that GUK.6 overexpression plays an important role in *** the expression of GRK6 maybe helpful in early diagnosis and prognosis of HCC.

关键词： Hepatocellular carcinoma GRK6 Ki-67

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Profiling and characterization of SARS-CoV-2 mutants’infectivity and antigenicity

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Signal Transduction and Targeted Therapy 2020年第1期5卷 899-900页

作者： Lin Wang Ling Wang Hui Zhuang department of microbiology and infectious disease center School of Basic Medical SciencesPeking University Health Science CenterBeijingChina

Using high-throughput pseudovirus assay in conjunction with neutralizing antibodies,Wang et *** 80 natural variants and 26 glycosylation-spike(S)mutants of SARS-CoV-2 in terms of infectivity and antigenicity.1 They identified several mutations that can critically affect the virus infectivity and reactivity to neutralizing antibodies(Fig.1).This study provides abundant and comprehensive data that will help us better understand the impact of mutations in S protein,and may contribute to future design of potent vaccine candidate and monoclonal antibodies(mAbs).

关键词： al infect vaccine

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Comparison of Abbott and Da-an real-time PCR for quantitating serum HBV DNA

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World Journal of Gastroenterology 2014年第33期20卷 11762-11769页

作者： Ning Qiu Rui Li Jian-Guo Yu Wen Yang Wei Zhang Yong An Tong Li Xue-En Liu Hui Zhuang department of microbiology and infectious disease center School of Basic Medical Sciences Peking University Health Science Center department of Internal Medicine Liver Disease Center No. 88 Hospital of People’s Liberation Army

AIM: To compare the performance of the Da-an real-time hepatitis B virus (HBV) DNA assay and Abbott RealTime HBV assay.

关键词： Hepatitis B virus Hepatitis B virus DNA quantitation Real-time polymerase chain reaction Chronic hepatitis B Antiviral therapy

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Antarctic thermolabile uracil-DNA-glycosylase- supplemented multiple cross displacement amplification using a label-based nanoparticle lateral flow biosensor for the simultaneous detection of nucleic acid sequences and elimination of carryover contamination

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Nano Research 2018年第5期11卷 2632-2647页

作者： Yi Wang Hui Li Yan Wang Huaqing Xu Jianguo Xu Changyun Ye State Key Laboratory of infectious disease Prevention and Control National Institute for Communicable Disease Control and Prevention Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Chinese Center for Disease Control and Prevention Beijing 102205 China department of microbiology Guizhou Medical University Guiyang 550004 China The Sixth People's Hospital of Zhengzhou Zhengzhou 450000 China

Here, we report a novel and universal methodology,termed ＂ntarctic thermolabile uracil-DNA-glycosylase （AUDG）-supplemented nucleic acid amplification techniques （NAAs） using a labeled-based nanoparticle lateral flow biosensor （LFB）＂（AUDG-NAAs-LFB）, which merges enzymatic （AUDG） digestion of contaminant amplicons with different nucleic acid amplification techniques （NAAs）, and uses a lateral flow biosensor （LFB） for the rapid and visual confirmation of the presence of a target nucleic acid sequence. AUDG-NNAs-LFB is a one-pot, closedvessel assay, that can effectively eliminate false-positive signals arising from either carryover contaminants or the interaction between labeled primers. A new LFB was devised for detecting three targets （two amplicons generated from amplification of target sequences, and a chromatography control）, without the need for probe- hybridization or additional incubation steps. As a proof of concept, multiple cross displacement amplification （MCDA）, which is a specific, sensitive, and rapid isothermal amplification method, was selected as the model amplification technique to demonstrate the feasibility of AUDG-NAAs-LFB. As a result, we demonstrate the applicability of the AUDG-MCDA-LFB method for simultaneously detecting high-risk human papillomaviruses genotypes 16 and 18, which are the most and second-most prevalent strains of the virus reported in women worldwide. We also confirm the principle behind the AUDG-MCDA- LFB assay and validate its sensitivity, reproducibility, and specificity using serial dilutions of the type-specific plasmids, as well as clinical samples. This proof- of-concept method （AUDG-MCDA-LFB） can be easily reconfigured to detect various nudeic acid sequences by redesigning the specific MCDA primers.

关键词： Antarctic thermolabile uracil-DNA-glycosylase(AUDG) nucleic acid amplification techniques (NAAs) multiple cross displacement amplification (MCDA) lateral flow biosensor (LFB) limit of detection (LOD) human papillomaviruses(HPV)

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