Expression of an engineered soluble coxsackievirus and adenovirus receptor by a dimeric AAV9 vector inhibits adenovirus infection in mice
Expression of an engineered soluble coxsackievirus and adenovirus receptor by a dimeric AAV9 vector inhibits adenovirus infection in mice
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二聚体 AAV9 载体表达工程化可溶性柯萨奇病毒和腺病毒受体可抑制小鼠体内的腺病毒感染
DOI：
10.1038/gt.2015.19
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发表时间：
2015
期刊：
影响因子：
5.1
通讯作者：
Fechner H
中科院分区：
文献类型：
--
作者：
Röger C;Pozzuto T;Klopfleisch R;Kurreck J;Pinkert S;Fechner H
免疫抑制(IS)患者，如造血干细胞移植的接受者，偶尔会发生严重和致命的腺病毒(Ad)感染。在这里，我们分析了基于可溶柯萨奇病毒和Ad受体(SCAR)的病毒受体陷阱(SCAR)抑制Ad感染的潜力。在体外，在细胞培养中表达了由CAR胞外区和人IgG1Fc部分组成的二聚体融合蛋白SCAR-Fc和缺少Fc结构域的单体SCAR。细胞培养上清液中分泌的SCAR比SCAR-FC多，但其Ad中和活性低于SCAR-FC。进一步的研究表明，SCAR-FC可将Ad的感染降低100倍，并将其诱导的细胞毒性降低约20倍。在感染之前应用SCAR-FC不仅可以抑制Ad感染，而且当用于治疗持续的Ad感染时，它也可以抑制感染。在体内，通过AAV9载体将SCAR-Fc导入IS小鼠，获得持续的高水平(>；40μg ml−1)SCAR-Fc血清。SCAR-Fc血清浓度足以显著抑制肝脏和心脏野生型Ad5感染。使用SCAR-FC治疗没有引起副作用。因此，SCAR-Fc病毒受体TRAP可能是治疗Ad感染的一种有前途的新疗法。
Immunosuppressed (IS) patients, such as recipients of hematopoietic stem cell transplantation, occasionally develop severe and fatal adenovirus (Ad) infections. Here, we analyzed the potential of a virus receptor trap based on a soluble coxsackievirus and Ad receptor (sCAR) for inhibition of Ad infection. In vitro, a dimeric fusion protein, sCAR-Fc, consisting of the extracellular domain of CAR and the Fc portion of human IgG1 and a monomeric sCAR lacking the Fc domain, were expressed in cell culture. More sCAR was secreted into the cell culture supernatant than sCAR-Fc, but it had lower Ad neutralization activity than sCAR-Fc. Further investigations showed that sCAR-Fc reduced the Ad infection by a 100-fold and Ad-induced cytotoxicity by~ 20-fold. Not only was Ad infection inhibited by sCAR-Fc applied prior to infection, it also inhibited infection when used to treat ongoing Ad infection. In vivo, sCAR-Fc was delivered to IS mice by an AAV9 vector, resulting in persistent and high (> 40 μg ml− 1) sCAR-Fc serum levels. The sCAR-Fc serum concentration was sufficient to significantly inhibit hepatic and cardiac wild-type Ad5 infection. Treatment with sCAR-Fc did not induce side effects. Thus, sCAR-Fc virus receptor trap may be a promising novel therapeutic for treatment of Ad infections.
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影响因子：
11.8
作者：
Schilham, MW;Claas, EC;van Tol, MJ
通讯作者：
van Tol, MJ
环磷酰胺诱导的小鼠膀胱炎中白细胞介素 6 基因表达的上调：原位杂交组织化学研究。
DOI：
--
发表时间：
2006
期刊：
Internatonal Journal of Urology 13(10)
影响因子：
--
作者：
Nishii H;Nomura M;Fujimoto N;Matsumoto T
通讯作者：
Matsumoto T
影响因子：
3.8
作者：
Jimenez-Clavero, MA;Escribano-Romero, E;Spiller, OB
通讯作者：
Spiller, OB
影响因子：
8.8
作者：
Kajon, Adriana E.;Dickson, Laura M.;Hodinka, Richard L.
通讯作者：
Hodinka, Richard L.
影响因子：
5.4
作者：
Shafren, DR;Dorahy, DJ;Barry, RD
通讯作者：
Barry, RD