柯萨奇病毒（Coxsachievirus）是一种肠病毒（enteroviruses）分为A和B两类，是一类常见的经呼吸道和消化道感染人体的病毒，感染后人会出现发热、打喷嚏、咳嗽等感冒症状。妊娠期感染可引起非麻痹性脊髓灰质炎性病变，并致胎儿宫内感染和致畸。

牛磺酸对感染柯萨奇B3病毒大鼠心肌细胞L型电压依赖性钙通道的影响
Effects of taurine on L-type voltage-dependent Ca2+ channel in rat cardiomyocytes infected with coxsackievirus B3.
<<中国药理学报>>1998年 第19卷 第03期
作者: 郭棋, 刘艳红, 顾全保, 杨英珍, 刘恭鑫, 期刊 QCode : zgylxb199803009
目的: 观察牛磺酸对正常和感染柯萨奇B3病毒大鼠心肌细胞L型钙通道的影响. 　方法: 用膜片箝技术记录经L型钙通道的Ca2+电流. 　结果: 正常心肌细胞L型钙通道的Ca2+电流密度为4.1±0.8 pA/pF, 柯萨奇B3病毒感染后Ca2+电流密度增加到4.9±1.4 pA/pF. 　牛磺酸16 mmol.L-1不仅使正常心肌细胞L型钙通道的Ca2+电流密度降为3.5±0.5 pA/pF, 也使感染柯萨奇B3病毒后心肌细胞的Ca2+电流密度降为3.8±0.8 pA/pF. 　柯萨奇B3病毒感染使引起{zd0}Ca2+电流的膜电压(Vp)由8±8 mV减为5±3 mV, 牛磺酸可使降低的Vp恢复到8±4 mV. 　结论: 牛磺酸抑制柯萨奇B3病毒感染引起的Ca2+电流的增加, 并使因感染而降低的引起{zd0}Ca2+电流的膜电压正常化. 　牛磺酸对L型钙通道的影响是牛磺酸减轻病毒感染引起的细胞内Ca2+增加和异常电活动的机制之一.
关键词: 心肌, 钙通道, 柯萨奇B病毒, 牛磺酸, 膜片箝技术,
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《中国应用生理学杂志》 1999年03期  
柯萨奇B_3病毒对心肌细胞离子通道电流的影响

鲍伟胜 刘恭鑫 杨英珍 王春雷
【摘要】：目的 :探讨柯萨奇B3病毒 (coxsackievirusB3,CVB3)对大鼠心肌细胞离子通道的影响 ,以了解病毒感染导致细胞电生理活动异常的机理。方法 :酶消化法获得单个心肌细胞后利用膜片钳全细胞电流记录技术观察CVB3对L型钙通道电流、钠通道电流、外向钾电流和内向整流性钾电流的影响。结果 :CVB3感染使L型钙通道电流、外向钾电流增加 ,内向整流性钾电流减小 ,对钠通道电流无明显影响。结论 :CVB3对L型钙通道电流、外向钾电流和内向整流性钾电流的影响可能是病毒感染后细胞损伤和产生异常电活动的原因。

【作者单位】： 上海医科大学附属中山医院!上海市心血管病研究所 卫生部病毒性心脏病重点实验室 上海200032 上海医科大学附属中山医院!上海市心血管病研究所 卫生部病毒性心脏病重点实验室 上海200032 上海医科大学附属中山医院!上海市心血管病研究所 卫生部病毒性心脏病重点实验室 上海2000
【关键词】： 柯萨奇B_病毒 L型钙通道电流 钠通道电流 钾通道电流
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Chin Med Sci J. 2000 Sep;15(3):150-3.

Effect of coxsackievirus b3 on ion channel currents in rat ventricular myocytes.
Bao W, Liu G, Wang C, Yang Y, Guo Q, Yu Y.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital of Shanghai Medical University, Shanghai 200032.

Abstract
OBJECTIVE: To investigate the effects of coxsackievirus B3(CVB3) on ion channel currents in rat ventricular myocytes. METHODS: Rat hearts were isolated with collagenase to acquire single ventricular myocytes, L-type voltage-dependent calcium channel (VDCC) current (I(Ca)), Na+ current (I(Na)), outward potassium current (I(out)), inwardly rectifying potassium current(I(KI)) were recorded using whole cell patch clamp techniques. RESULTS: CVB3 infection increased I(Ca) and I(out), while decreased I(KI); but it had no obvious effect on I(Na). CONCLUSION: The effects of CVB3 an I(Ca), I(out), I(KI) may be one of the mechanisms of myocytes damage and the occurrence of abnormal electroactivities induced by CVB3 infection.
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柯萨奇B3病毒对心肌细胞钙平衡的影响

<<中华实验和临床病毒学杂志>>2000年 第14卷 第2期
作者: 刘恭鑫, 杨英珍, 顾全保,

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柯萨奇病毒B3感染培养大鼠心室肌细胞L-型钙通道mRNA表达的变化
Changes of L-calcium channel subunits mRNA expression in rat cultured ventricular myocytes infected by coxsackievirus B3
<<中国分子心脏病学杂志>>2003年 第3卷 第03期
作者: 黄淑君, 田苗, 廖玉华,          期刊 QCode : zgfzxzbxzz200303008
目的:观察柯萨奇病毒B3感染对培养大鼠心室肌细胞L-型钙通道mRNA表达的影响.方法:用柯萨奇病毒B3感染原代培养新生大鼠心室肌细胞,合成大鼠心室肌细胞L-型钙通道各亚单位引物,通过逆转录-聚合酶链反应技术,以β-actin为内参照,测量钙通道各亚单位mRNA表达量在病毒感染前后的变化.结果:病毒感染组心室肌细胞L-型钙通道α1(4.00±0.07 vs 2.21±0.41,p＜0.01),β(2.06±0.06 vs 1.22±0.30,p＜0.05)亚单位mRNA表达量较正常对照组显著增加,而α2/δ(4.12±0.19 vs 4.13±0.27,P＞0.05)亚单位mRNA表达量变化无统计学意义.结论:柯萨奇病毒B3感染心室肌细胞钙通道mRNA表达量增加,可能是病毒介导心室肌细胞L-型钙电流变化的分子基础.

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心肌细胞感染病毒后钙、钾通道电流及其表达改变和牛磺酸的作用
<<中华心血管病杂志>>2003年 第31卷 第2期
作者: 宿燕岗, 杨英珍, 鲍伟胜, 刘恭鑫, 葛均波, 陈灏珠,

中华医学会 QCode : zhxxgb200302016
目的观察心肌细胞感染病毒后心肌细胞钙、钾通道电流及通道表达改变和牛磺酸的作用.方法 (1)体外心肌细胞感染病毒:用胰蛋白酶和胶原酶消化法分别获得大鼠、乳鼠培养和分离的心肌细胞并感染柯萨奇B3病毒,用于检测Ca2+跨膜内流、电压依赖性钙通道电流(ICa)和外向钾通道电流(Iout).(2)在体小鼠感染病毒:BALB/c小鼠腹腔内注射柯萨奇B3病毒 7d后取出心脏用于检测电压依赖性钙通道α1亚单位抗原和电压调控性钾通道(Kv)mRNA的表达.相应各组加入不同剂量的牛磺酸并观察其作用.结果 (1)感染柯萨奇B3病毒后Ca2+跨膜内流量及ICa增加,牛磺酸对其有抑制作用.(2)柯萨奇B3病毒感染使Iout明显增大,牛磺酸可使病毒感染后的Iout趋于恢复正常.(3)柯萨奇B3病毒感染后小鼠心肌出现强电压依赖性钙通道α1亚基抗原阳性信号,Kv1.2、Kv2.1、Kv4.2 mRNA与3种探针的杂交信号亦明显增强,牛磺酸可使增强的阳性信号减弱.结论柯萨奇B3病毒感染后心肌细胞钙、钾离子通道电流及表达均增加,牛磺酸可通过抑制其改变而发挥对感染病毒心肌细胞的保护作用.
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The EMBO Journal (1997) 16, 3519 - 3532 doi:10.1093/emboj/16.12.3519
Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release

Frank J.M. van Kuppeveld1, Joost G.J. Hoenderop1, Rolf L.L. Smeets2, Peter H.G.M. Willems2, Henri B.P.M. Dijkman3, Jochem M.D. Galama1 and Willem J.G. Melchers1

Department of Medical Microbiology, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Department of Biochemistry, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Department of Pathology, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Received 8 October 1996; Revised 12 March 1997

Abstract
Digital-imaging microscopy was performed to study the effect of Coxsackie B3 virus infection on the cytosolic free Ca2+ concentration and the Ca2+ content of the endoplasmic reticulum (ER). During the course of infection a gradual increase in the cytosolic free Ca2+ concentration was observed, due to the influx of extracellular Ca2+. The Ca2+ content of the ER decreased in time with kinetics inversely proportional to those of viral protein synthesis. Individual expression of protein 2B was sufficient to induce the influx of extracellular Ca2+ and to release Ca2+ from ER stores. Analysis of mutant 2B proteins showed that both a cationic amphipathic -helix and a second hydrophobic domain in 2B were required for these activities. Consistent with a presumed ability of protein 2B to increase membrane permeability, viruses carrying a mutant 2B protein exhibited a defect in virus release. We propose that 2B gradually enhances membrane permeability, thereby disrupting the intracellular Ca2+ homeostasis and ultimately causing the membrane lesions that allow release of virus progeny.

Keywords:endoplasmic reticulum, enterovirus, intracellular calcium concentration, virus–host interactions
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The Coxsackievirus 2B Protein Suppresses Apoptotic Host Cell Responses by Manipulating Intracellular Ca2+ Homeostasis*
Michelangelo Campanella‡, Arjan S. de Jong§, Kjerstin W. H. Lanke§, Willem J. G. Melchers§, Peter H. G. M. Willems¶, Paolo Pinton‡, Rosario Rizzuto‡∥ and Frank J. M. van Kuppeveld§**
First Published on February 19, 2004, doi: 10.1074/jbc.M309494200
April 30, 2004 The Journal of Biological Chemistry, 279, 18440-18450.
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Enterovirus protein 2B po(u)res out the calcium: a viral strategy to survive?
Frank J.M. van Kuppevelda, *, , Arjan S. de Jonga, Willem J.G. Melchersa and Peter H.G.M. Willemsb

Available online 22 December 2004. Trends in Microbiology
Volume 13, Issue 2, February 2005, Pages 41-44
Enteroviruses modify several cellular functions to ensure efficient replication. However, some of these alterations can trigger a defensive apoptotic host-cell program. To prevent premature abortion of their productive cycle, enteroviruses have developed anti-apoptotic countermeasures. Here, we discuss recent evidence that the enterovirus 2B protein exerts an anti-apoptotic activity that is related to its ability to form pores in endoplasmic reticulum (ER) and Golgi membranes, thereby reducing their Ca2+ content and perturbing ER–mitochondrial Ca2+ signaling.

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J Biol Chem. 2006 May 19;281(20):14144-50. Epub 2006 Mar 15.

The coxsackievirus 2B protein increases efflux of ions from the endoplasmic reticulum and Golgi, thereby inhibiting protein trafficking through the Golgi.
de Jong AS, Visch HJ, de Mattia F, van Dommelen MM, Swarts HG, Luyten T, Callewaert G, Melchers WJ, Willems PH, van Kuppeveld FJ.

Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract
Coxsackievirus infection leads to a rapid reduction of the filling state of the endoplasmic reticulum (ER) and Golgi Ca2+ stores. The coxsackievirus 2B protein, a small membrane protein that localizes to the Golgi and to a lesser extent to the ER, has been proposed to play an important role in this effect by forming membrane-integral pores, thereby increasing the efflux of Ca2+ from the stores. Here, evidence is presented that supports this idea and that excludes the possibility that 2B reduces the uptake of Ca2+ into the stores. Measurement of intra-organelle-free Ca2+ in permeabilized cells revealed that the ability of 2B to reduce the Ca2+ filling state of the stores was preserved at steady ATP. Biochemical analysis in a cell-free system further showed that 2B had no adverse effect on the activity of the sarco/endoplasmic reticulum calcium ATPase, the Ca2+-ATPase that transports Ca2+ from the cytosol into the stores. To investigate whether 2B specifically affects Ca2+ homeostasis or other ion gradients, we measured the lumenal Golgi pH. Expression of 2B resulted in an increased Golgi pH, indicative for the efflux of H+ from the Golgi lumen. Together, these data support a model that 2B increases the efflux of ions from the ER and Golgi by forming membrane-integral pores. We have demonstrated that a major consequence of this activity is the inhibition of protein trafficking through the Golgi complex.

PMID: 16540472 [PubMed - indexed for MEDLINE

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Functional and Structural Characterization of 2B Viroporin Membranolytic Domains
Silvia Snchez-Martnez‡, Nerea Huarte‡, Rubn Maeso‡, Vanessa Madan§, Luis Carrasco§ and JosL. Nieva*‡
Unidad de Biofsica (CSIC-UPV/EHU) and Departamento de Bioqumica, Universidad del Pas Vasco, Aptdo. 644, 48080 Bilbao, Spain, and Centro de Biologa Molecular (CSIC-UAM), Universidad Autnoma de Madrid, Canto Blanco, 28049 Madrid, Spain
Biochemistry, 2008, 47 (40), pp 10731–10739
DOI: 10.1021/bi800997a
Publication Date (Web): September 12, 2008