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携带人5型腺病毒纤维蛋白细胞结合结构域的绵羊腺病毒的嗜性改变

Altered tropism of an ovine adenovirus carrying the fiber protein cell binding domain of human adenovirus type 5.

作者信息

Xu Z Z, Both G W

机构信息

Molecular Science, Commonwealth Scientific and Industrial Research Organization, North Ryde, 2113, Australia.

出版信息

Virology. 1998 Aug 15;248(1):156-63. doi: 10.1006/viro.1998.9261.

DOI:10.1006/viro.1998.9261
PMID:9705265
Abstract

Ovine adenovirus OAV287 (OAV) is phylogenetically and serotypically distinct from human Ad5. OAV grows productively in CSL503 foetal ovine lung cells and abortively infects several human cell lines. OAV has a unique fiber and a penton protein that lacks a recognisable integrin-binding motif. It is not known whether a secondary receptor is required for infection. A hybrid virus was constructed in which the cell binding domain on the OAV fiber protein was exchanged for the equivalent region from human adenovirus type 5. The hybrid OAV grew to titres that were 1 to 2 log10 lower than wild-type OAV in permissive ovine cells. Human Ad5 also infected CSL503 cells but failed to compete with OAV for receptor binding sites on those cells. However, the hybrid virus did compete with Ad5, consistent with its use of the Ad primary receptor. The hybrid virus was also neutralised by Ad5 antiserum whereas OAV was not. Human 293 kidney and LNCaP prostate cell lines that were not detectably infected by OAV were infected by the hybrid virus and other human prostate and breast cancer cell lines showed greatly enhanced infectivity. Thus, modification of the fiber cell binding domain was sufficient to profoundly alter the tropism of OAV, suggesting that the interaction between the primary receptor and the virus particle is the major factor controlling virus entry during infection.

摘要

绵羊腺病毒OAV287(OAV)在系统发育和血清型上与人类腺病毒5型(Ad5)不同。OAV能在CSL503绵羊胎儿肺细胞中有效生长,并能流产感染多种人类细胞系。OAV有独特的纤维和五聚体蛋白,缺乏可识别的整合素结合基序。目前尚不清楚感染是否需要辅助受体。构建了一种杂交病毒,其中OAV纤维蛋白上的细胞结合域被替换为人腺病毒5型的相应区域。在允许的绵羊细胞中,杂交OAV的生长滴度比野生型OAV低1至2个对数10。人类Ad5也能感染CSL503细胞,但无法与OAV竞争这些细胞上的受体结合位点。然而,杂交病毒确实能与Ad5竞争,这与其使用Ad主要受体一致。杂交病毒也能被Ad5抗血清中和,而OAV则不能。未被OAV明显感染的人类293肾细胞和LNCaP前列腺细胞系能被杂交病毒感染,其他人类前列腺和乳腺癌细胞系的感染性也大大增强。因此,纤维细胞结合域的修饰足以深刻改变OAV的嗜性,这表明主要受体与病毒颗粒之间的相互作用是感染过程中控制病毒进入的主要因素。

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