Coxsackie B viruses and the kidney--a neglected topic.

Coxsackie B viruses types 1-6 (CVB1-6) occur worldwide and cause a broad spectrum of diseases, including myocarditis and aseptic meningitis. Although renal damage due to CVB has been suspected since the 1950s, these agents are only rarely searched for in today's clinical nephrological practice. Nevertheless, CVB can infect mesangial cells. Furthermore, infections with these viruses lead to a histological picture resembling mesangioproliferative glomerulonephritis and IgA-nephropathy in mice. In the present article, we provide an overview of this largely neglected topic, and of the slowly and steadily increasing evidence suggesting a link between coxsackieviral infections and kidney diseases.     

The antiviral effect of jiadifenoic acids C against coxsackievirus B3

Coxsackievirus B type 3 (CVB3) is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM) and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs). The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.KEY WORDS: CVB3, Jiadifenoic acids C, Antiviral activityAbbreviations: CAR, coxsackievirus and adenovirus receptor; CPE, cytopathic effect; CVB3, coxsackievirus B type 3; CVBs, coxsackie B viruses; DAF, decay accelerating factor; DCM, dilated cardiomyopathy; IC₅₀, 50% inhibitory concentration; IRES, internal ribosomal entry site; MOI, multiplicity of infection; NTR, non-translated region; RBV, ribavirin; RdRp, RNA-dependent RNA polymerase; SI, selectivity index; Vero, African green monkey kidney cells     

黄芪皂甙对CVB_3病毒引起Vero细胞凋亡的研究

目的：细胞水平上建立病毒性心肌炎（Viral Myocarditis,VMC）模型,通过相关实验得出黄芪皂甙（total extract astragalus,TEA）具有抗病毒能力,进一步明确VMC发病过程中是否存在细胞凋亡以及黄芪皂甙是否能够抑制细胞凋亡。方法：体外培养Vero细胞和出生1-3 d乳鼠心肌细胞,通过细胞病变抑制实验、病毒繁殖抑制实验测定黄芪皂甙抗病毒能力,采用AnnexinV-FITC染色观察VMC发病过程中心肌细胞是否有凋亡,采用流式细胞仪检测TEA是否抑制细胞凋亡。结果：通过MTT染色分析发现TEA可有效保护细胞免受CVB3病毒侵袭,病毒繁殖抑制实验显示中、高剂量组TCID50比病毒组相差一个以上对数值,且TEA对细胞凋亡有抑制作用。结论：实验证实黄芪皂甙对心肌细胞有一定的保护作用,并且在VMC发病过程中存在细胞凋亡,且TEA能抑制心肌细胞凋亡。     

CAR在柯萨奇B3病毒感染心肌细胞中作用

目的探讨柯萨奇病毒和腺病毒受体(coxsackievirusandadenovirusreceptor,CAR)在嗜心性柯萨奇B3病毒(myocarditiccoxsaekievirusB3,CVB3m)感染心肌细胞中的作用。方法采用体外培养新生小鼠心肌细胞方法,建立CVB3m感染心肌细胞模型,将培养48h的心肌细胞分为对照组、CVB3m组和CAR抗体 CVB3m组,并作相应处理,继续培养48h后,分别观察各组心肌细胞病变效应(cytopathiceffect,CPE),并用四唑盐(MTT)比色法测定各组心肌细胞存活力。结果CAR抗体 CVB3m组心肌细胞CPE明显减轻,存活力显著增强,与CVB3m组比较差异显著(P<0.01),与对照组比较差异无显著性(P>0.05)。结论CAR抗体对CVB3m感染心肌细胞具有保护作用,提示CAR在CVB3m感染心肌细胞中可能发挥重要的介导作用。     

检测IgM及IgG抗体在病毒性心肌炎诊断中的意义

应用ＥＬＩＳＡ法对６３例刀性心肌炎患儿及９７例健康儿童血清进行检测，两组抗ＣＶＢＩｇＭ抗体阳性率分别为２１．６９％及７．２２％，有非常显著怀差别（Ｐ〈０．０１），而抗ＣＶＢ４ＩｇＭ抗体阳经分别为８７．９５％及７９．８３％，无显著性差别（Ｐ〈０．０５）。结果表明，检测单份血清抗ＣＶＢＩｇＭ抗体作为ＣＶＢ引起心肌炎的病因诊断指标。     

氧化苦参碱对病毒性心肌炎小鼠心肌细胞凋亡及相关因子的影响

目的 探讨氧化苦参碱(oxymatrine,OMT)对病毒性心肌炎小鼠心肌细胞凋亡及其凋亡相关因子蛋白表达的影响。方法 42只BALB/c小鼠随机分为正常对照组(NC)、病毒性心肌炎模型组(VM)、OMT高剂量组(OMT-H,25?mg·kg^-1·d^-1)、OMT中剂量组(OMT-M,12.5 mg·kg^-1·d^-1)、OMT低剂量组(OMT-L,6.25 mg·kg^-1·d^-1)、OMT极低剂量组(OMT-EL,3.125 mg·kg^-1·d^-1)、利巴韦林对照组(RB,100 mg·kg^-1·d^-1)。病毒性心肌炎小鼠由柯萨奇病毒B3型腹腔注射感染所致,各治疗组从末次给予病毒24 h后开始,腹腔注射,每日1次。于治疗第12天,每组处死小鼠6只,留取心肌标本。TUNEL法检测心肌细胞凋亡情况,免疫印迹法和免疫组织化学法检测Bcl-2和Bax蛋白的表达情况。结果 OMT治疗显著降低了病毒性心肌炎小鼠凋亡心肌细胞的数量,与病毒性心肌炎模型组比较,OMT-L组效果最佳(P<0.01)。与病毒性心肌炎模型组小鼠比较,OMT治疗组的小鼠心肌组织中Bax蛋白表达降低,而Bcl-2蛋白表达没有明显改变。结论 氧化苦参碱可减少病毒性心肌炎小鼠心肌细胞的凋亡,该作用与下调Bax蛋白表达有关。     

2011-2013年龙岩市手足口病流行病学 及病原学特征分析

摘要:目的　分析2011-2013年龙岩市手足口病（HFMD）流行病学和病原学特征。方法　运用描述流行病学方法对龙岩市2011-2013年HFMD资料进行分析。选取部分经实时荧光RT-PCR法检测,其他肠道病毒（Enterovirus,EV）阳性咽拭标本,用人横纹肌肉瘤（RD）细胞进行病毒分离,用RT-PCR法进行检测、序列测定和同源性分析,对分离到的病毒进行分析鉴定。结果　2011-2013年龙岩市HFMD发病率均处于较高水平。发病高峰出现在5-7月,男性多于女性。＜5岁儿童病例占报告总病例的93.6%,散居儿童占75.4%。104份其他EV阳性标本病毒分离培养物,经RT-PCR法检测EV阳性88份（84.6%）,其中29份肠道病毒71型（EV71）阳性,4份EV71和柯萨奇病毒A16型（CVA16）同时阳性,3份柯萨奇病毒B5型（CVB5）阳性,2份柯萨奇病毒A10型（CVA10）阳性,50份EV阳性培养物仍未能分型。分离到的EV71型属于C4a基因亚型。CVA16型属于B1b基因型。结论　龙岩市HFMD 疫情处于高流行态势,＜5岁散居儿童是主要发病人群,病原仍以EV71和CVA16为主,同时发现了CVB5和CVA10病毒。     

Myocarditis

Myocarditis is an uncommon, potentially life-threatening disease that presents with a wide range of symptoms in children and adults. Viral infection is the most common cause of myocarditis in developed countries, but other etiologies include bacterial and protozoal infections, toxins, drug reactions, autoimmune diseases, giant cell myocarditis, and sarcoidosis. Acute injury leads to myocyte damage, which in turn activates the innate and humeral immune system, leading to severe inflammation. In most patients, the immune reaction is eventually down-regulated and the myocardium recovers. In select cases, however, persistent myocardial inflammation leads to ongoing myocyte damage and relentless symptomatic heart failure or even death. The diagnosis is usually made based on clinical presentation and noninvasive imaging findings. Most patients respond well to standard heart failure therapy, although in severe cases, mechanical circulatory support or heart transplantation is indicated. Prognosis in acute myocarditis is generally good except in patients with giant cell myocarditis. Persistent, chronic myocarditis usually has a progressive course but may respond to immunosuppression.     

穿孔素在慢性心肌损伤中的表达及其意义

目的：探讨穿孔素在阿萨奇病毒B组3型（CVB3m)至T－2毒素染毒小鼠心肌损伤中的表达及其意义,方法：实验组BALB／C小鼠1．0mg/kg体重T－2毒素隔日灌胃,3周后腹腔接种0．1ml内含1000TCID50的CVB3m病毒液,对照组生理盐水灌胃,腹腔接种0．1ml 1640营养液,观察心肌病理改变,同时用RTPCR技术对心肌组织中CVB3m RNA和穿孔素mRNA表达进行检测,结果：CVB3m感染T－2毒素染毒小鼠心肌出现慢性损伤,可见纤维结缔组织增生和坏死灶癜痕修复。心肌组织中持续表达CVB34m RNA和穿孔素mRNA。结论CVB3m RNA和穿孔素mRNA的持续表达可能是CVB3m致T－2毒素染毒小鼠心肌慢性损伤的机制之一。     

柯萨奇B3m病毒致低硒低维生素E鼠心肌损伤的实验研究

目的 探讨柯萨奇（CV）B3m感染低Se低VE鼠心肌损伤的发病特点。方法 1周龄乳鼠分别给予低Se低VE和补Se常VE饲料喂养,4周后腹腔接种病毒,对照组接种等量PRMI1640培养液,7d后处死,光镜下观察心肌的病理改变。结果 CVB3m感染的Se和VE均缺乏鼠的心肌病变检出率为93．3％,病变为多发性大面积灶状坏死,融合成片,炎性细胞较少浸润,与急性克山病的病理改变类似;而补Se常VE组仅见散发间质炎性灶,面积较小,伴有大量的炎细胞,检出率为16．7％。结论 低硒低维生素E状态下,柯萨奇病毒B3m可显著加重小鼠的心肌损伤。