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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun Yi Sangmi Jun Bum-Tae Kim Jong-Won Oh aleem siddiqui Seong-Jun Kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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Subversion of cellular autophagy during virus infection:Insights from hepatitis B and hepatitis C viruses

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Liver Research 2018年第3期2卷 146-156页

作者： Mohsin Khan Hasan Imam aleem siddiqui Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCAUSA

Autophagy is a self-eating process,in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular *** is generally thought of as a pro-survival mechanism which is not only important for balancing energy supply at times of nutrient deprivation but also in the removal of various stress stimuli to ensure *** addition to the target materials of“self”origin,autophagy can also eliminate intracellular pathogens and acts as a defense mechanism to curb *** addition,autophagy is linked to the host cell's innate immune ***,viruses have evolved various strategies to manipulate and overtake host cell machinery to establish productive replication and maintain infectious *** fact,replication of many viruses has been found to be autophagy-dependent and suppression of autophagy can potentially affect the viral ***,autophagy can either serve as an anti-viral defense mechanism or a pro-viral process that supports viral *** B virus(HBV)and hepatitis C virus(HCV)are known to co-opt cellular autophagy process as a pro-viral *** viruses also induce mitophagy,which contributes to the establishment of chronic *** review focuses on the roles of autophagy and mitophagy in the chronic liver disease pathogenesis associated with HBV and HCV infections.

关键词： Autophagy Hepatitis B virus(HBV) Hepatitis C virus(HCV) Endoplasmic reticulum(ER)stress Mitophagy

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乙型肝炎病毒X蛋白通过氧化应激引起Raf-1线粒体转位

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中华肝脏病杂志 2008年第4期16卷 319-320页

作者：陈军 aleem siddiqui 中南大学湘雅二医院感染科长沙410011 Department of Medicine University of CaliforniaSan Diego

HBV慢性感染是诱发肝细胞癌（HCC）的首要因素之一，在HBV DNA的开放读码区S、C、P、X中，HBx基因及其所编码蛋白与HCC的关系最为密切，但它在转录活化中的具体机制和对病毒生命周期的影响的确切机制仍未明了，有待更深入的研究。而Raf-... 详细信息

HBV慢性感染是诱发肝细胞癌（HCC）的首要因素之一，在HBV DNA的开放读码区S、C、P、X中，HBx基因及其所编码蛋白与HCC的关系最为密切，但它在转录活化中的具体机制和对病毒生命周期的影响的确切机制仍未明了，有待更深入的研究。而Raf-1作为原癌基因，对肿瘤的形成和发展起着重要作用，在促进肿瘤细胞增殖的同时，作为抗凋亡基因，阻止细胞凋亡的发生。本研究试图探讨HBx诱导Raf-1线粒体转位的现象及其机制。

关键词：肝炎病毒乙型癌肝细胞细胞凋亡线粒体

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丙型肝炎病毒非结构蛋白5a对细胞周期的影响

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中华肝脏病杂志 2004年第1期12卷 47-48页

作者：龚国忠 aleem siddiqui 苏先狮中南大学湘雅二医院肝病研究中心长沙市410011 美国科罗拉多大学医学院微生物与分

丙型肝炎病毒(HCV)感染是慢性肝炎、肝硬化的主要病因之一,并与肝细胞癌的发生关系非常密切.但HCV导致原发性肝细胞癌的机制,特别是其基因产物(结构蛋白和非结构蛋白)在致癌中的作用仍不清楚.HCV非结构蛋白5A(NS5A)能激活多种转录因子,... 详细信息

丙型肝炎病毒(HCV)感染是慢性肝炎、肝硬化的主要病因之一,并与肝细胞癌的发生关系非常密切.但HCV导致原发性肝细胞癌的机制,特别是其基因产物(结构蛋白和非结构蛋白)在致癌中的作用仍不清楚.HCV非结构蛋白5A(NS5A)能激活多种转录因子,并与细胞内因子结合,影响其功能,导致细胞增殖分化异常,可能与原发性肝细胞癌的发生有关.为进一步探讨它们之间的联系,采用放线菌素D(Act.D)作用于HepG2肝癌细胞株研究HCV NS5A对细胞周期调控的影响,从而为阐明HCV参与肝细胞癌的分子机制积累更多的资料.

关键词：丙型肝炎病毒非结构蛋白5a HCV 细胞周期肝硬化

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MOLECULAR CLONING AND CHARACTERIZATION OF THE cDNA CODING FOR HEPATITIS B VIRUS SURFACE ANTIGEN

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Science China Chemistry 1985年第1期28卷 49-59页

作者：何葆光,JOSEPH L. MELNICK,aleem siddiqui,WILLIAM S. ROBINSON,SIMON W. LAW,EUGENE C. LAI Shanghai Institute of Biological Products Ministry of Public Health PRC Department of Virology and Epidemiology Baylor Colleye of Medicine USA Department of Medicine Stanford University School of Medicine USA Department of Medicine Stanford University School of Medicine USA Department of Cell Biology Baylor College of Medicine USA Department of Cell Biology Baylor College of Medicine USA

Hepatitis B virus surface antigen （HBsAg） inRNA has been enriched from a hepatoma cell line （PLC/PRF/5） by specific polysome immunoprecipitation and used for cDNA cloning. A HBsAg cDNA clone was identified by in situ hybridization with a cloned viral probe. It was characterized by restriction endonuclease mapping and DNA sequence analysis. Molecular hybridization of PLC/PRF/5 cellular DNA and RNA to [32P]-labeled HBsAg cDNA revealed the integration of at least six copies of the hepatitis B virus （HBV） DNA into the host genome and expression of three DNA species confining HBsAg-specific sequences. The possible role of HBV in the oncogenesis of primary hepatocellular carcinoma is discussed.

关键词： DNA RNA HBsAg MOLECULAR CLONING AND CHARACTERIZATION OF THE cDNA CODING FOR HEPATITIS B VIRUS SURFACE ANTIGEN

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乙型肝炎病毒X基因蛋白诱导人类白细胞抗原DR表达

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同济医科大学学报 1990年第6期19卷 361-365页

作者：胡克勤 John M Vierling 郝连杰 aleem siddiqui 同济医科大学附属同济医院临床免疫研究室美国科罗拉多大学医学院消化内科美国科罗拉多大学医学院微生物系

乙型肝炎病毒(HBV)所致的肝细胞坏死,被认为是与人类白细胞抗原(HLA)有关的MHC限制的T细胞为主的免疫应答的结果。本研究证实,转染HBV基因组或X基因后的人肝癌细胞系可诱导HLAⅡ(即HLA DR)表达。核转录及RNA杂交分析提示表达X基因的细胞... 详细信息

乙型肝炎病毒(HBV)所致的肝细胞坏死,被认为是与人类白细胞抗原(HLA)有关的MHC限制的T细胞为主的免疫应答的结果。本研究证实,转染HBV基因组或X基因后的人肝癌细胞系可诱导HLAⅡ(即HLA DR)表达。核转录及RNA杂交分析提示表达X基因的细胞其HLA DR mRNA水平增加,X蛋白增加该基因的转录。氯霉索乙酰基转移酶(CAT)基因分析进一步提示,X蛋白通过作用于HLA DR基因上游的调节序列诱导HLA DR表达。结果表明:X蛋白可能通过调节HLA DR表达参与HBV感染的免疫发病机理。

关键词：乙型肝炎病毒 X蛋白人白细胞抗原

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Massive ascites as a presenting manifestation of chronic lymphocytic leukemia

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World Journal of Gastroenterology 2008年第22期14卷 3594-3597页

作者： Neelam siddiqui Saeed Al-Amoudi Aamer aleem Maha Arafah Layla Al-Gwaiz Department of Medicine College of Medicine King Khalid University Hospital King Saud University Riyadh Saudi Arabia Department of Pathology College of Medicine King Khalid University Hospital King Saud University Riyadh Saudi Arabia

Ascites is not an uncommon manifestation of certain solid tumors like gastrointestinal malignancies, ovarian cancer and breast cancer. However, it is unusual to encounter ascites in patients with hematological malignancies especially chronic leukemia. The patient described here presented with massive ascites and blood lymphocytosis. Further studies confirmed the diagnosis of chronic lymphocytic leukemia with ascites. The ascitic fluid was exudative, consisting of mature-looking B-lymphocytes, which were morphologically and immunophenotypically similar to peripheral blood and bone marrow cells. The patient was treated with chemotherapy and achieved a good response and diminution of ascitic fluid accumulation.

关键词：慢性淋巴细胞白血病腹水癌症治疗方法

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