Porcine adenovirus serotype 3 internalization is independent of CAR and ανβ3 or ανβ5 integrin
Porcine adenovirus serotype 3 internalization is independent of CAR and ανβ3 or ανβ5 integrin
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DOI：
10.1016/j.virol.2004.11.010
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发表时间：
2005-02-05
期刊：
影响因子：
3.7
通讯作者：
Mittal, SK
中科院分区：
文献类型：
--
作者：
Bangari, DS;Mittal, SK
非人类腺病毒在内，包括猪腺病毒Scrotype 3（PAD3）是用于基因递送的新兴载体。 PAD3有效地转导人类和鼠类细胞在培养物中，并规避人类已经存在的体液免疫。 Coxsackievievirus-腺病毒受体（CAR）用作主要受体，α（V）β（3）或α（V）β（V）β（5）整联蛋白作为几种人腺病毒（包括HAD）的几种人腺病毒（HAT）亚型的次级受体。在这项研究中，我们推断了CAR，Alpha（V）Beta（3）或Alpha（V）β（5）整合素在PAD3内部化中的作用。使用复制缺陷的PAD-GFP（表达绿色荧光蛋白[GFP]）和HAD-GFP（HAD-GFP（HAD-GFP）（HASH HASH HASH HASH HASH HAS HASH HAS HASH HASH HAS HAST 3载体表达GFP），在人类乳腺上皮（MCF-10A）细胞中进行了转导实验。 MCF-10A细胞用或不带有抗人CAR或抗α（V）β（3）或抗α（V）β（V）β（5）整联蛋白抗体在感染HAD-GFP或PAD-GFP之前进行处理。与未处理的细胞相比，在抗体处理的细胞中观察到HAD-GFP转导的显着（P <0.05），而PAD-GFP的转导量保持在类似水平相似的水平。为了研究腺病毒纤维介导的病毒干扰，将MCF-10A细胞用或没有重组的HAS HADS或PAD3旋钮处理，然后再感染HAD-GFP或PAD-GFP。仅在同源载体的转导中观察到显着（p <0.05）的抑制作用。这些结果表明，PAB3的内在化是CAR的，并且α（V）β（3）或Alpha（V）β（5）beta（5）独立于HAD5和PAD3的主要受体是不同的。 CAR-和Alpha（V）β（3）或Alpha（V）β（5）PAD3载体的整合素独立于输入可能与其他腺病毒载体有效转导的细胞类型有关。 （c）2004 Elsevier Inc.保留所有权利。
Nonhuman adenoviruses including porcine adenovirus scrotype 3 (PAd3) are emerging vectors for gene delivery. PAd3 efficiently transduces human and murine cells in culture, and circumvents preexisting humoral immunity in humans. The coxsackievirus-adenovirus receptor (CAR) serves as a primary receptor and alpha(v)beta(3) or alpha(v)beta(5) integrin as a secondary receptor for several human adenovirus (HAd) subtypes including HAd5. In this study, we deduced the role of CAR, alpha(v)beta(3) or alpha(v)beta(5) integrin in PAd3 internalization. Transduction experiments were conducted in human mammary epithelial (MCF-10A) cells using replication-defective PAd-GFP (PAd3 vector expressing green fluorescent protein [GFP]) and HAd-GFP (HAd5 vector expressing GFP). MCF-10A cells were treated with or without anti-human CAR, or anti-alpha(v)beta(3) or anti-alpha(v)beta(5) integrin antibodies prior to infection with HAd-GFP or PAd-GFP. Significant (P < 0.05) inhibition in transduction by HAd-GFP was observed in antibody-treated cells as compared to untreated cells, whereas transduction by PAd-GFP remained to similar levels irrespective of the treatment. To study the adenoviral fiber knob-mediated virus interference, MCF-10A cells were treated with or without the recombinant HAd5 or PAd3 knob followed by infection with HAd-GFP or PAd-GFP. Significant (P < 0.05) inhibition was observed only in transduction of the homologous vector. These results suggested that PAB3 internalization was CAR- as well as alpha(v)beta(3) or alpha(v)beta(5) integrin-independent and the primary receptor for HAd5 and PAd3 were distinct. CAR- and alpha(v)beta(3) or alpha(v)beta(5) integrin-independent entry of PAd3 vectors may have implications in targeting cell types that are not efficiently transduced by other adenoviral vectors. (C) 2004 Elsevier Inc. All rights reserved.