HUMAN ADENOVIRUS-HOST CELL-INTERACTIONS - COMPARATIVE-STUDY WITH MEMBERS OF SUBGROUP-B AND SUBGROUP-C

HUMAN ADENOVIRUS-HOST CELL-INTERACTIONS - COMPARATIVE-STUDY WITH MEMBERS OF SUBGROUP-B AND SUBGROUP-C
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DOI:
10.1128/jvi.64.8.3661-3673.1990
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发表时间:
1990-08-01
影响因子:
5.4
通讯作者:
BOULANGER, P
BOULANGER, P
中科院分区:
医学2区
文献类型:
--
作者:
DEFER, C;BELIN, MT;BOULANGER, P

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在三个水平上比较分析了人腺病毒血清型B亚组(3型腺病毒[Ad 3]和Ad 7)和C亚组(Ad 2和Ad 5)的宿主细胞相互作用:(i)病毒颗粒与宿主细胞受体的结合;(ii)大分子与腺病毒粒子的共内化;和(iii)腺病毒诱导的细胞骨架改变。发现与人细胞受体的结合常数与Ad 2和Ad 3相似(8 × 10 - 4)。109至9倍109 M-1),每个细胞的受体位点数范围为5,000(Ad 2)至7,000(Ad 3)。亲和印迹、竞争实验和免疫荧光染色表明,B和C亚组成员的腺病毒受体位点不同。腺病毒颗粒增加了细胞对大分子物质的渗透性。我们发现,这种全局效应可以分为两个不同的事件:(i)大分子和病毒体共内化到胞吞囊泡中,这是一种以非依赖于病毒型的方式发生的现象,以及(ii)腺病毒诱导的内体膜裂解后大分子释放到细胞质中。后一个过程被发现是类型特异性的,并且需要血清型2或5的未改变的和感染性的病毒颗粒。波形蛋白丝网络的核周凝聚观察到在早期阶段的感染与Ad 2或Ad 5,但没有与Ad 3,Ad 7,和非感染性颗粒的Ad 2或Ad 5,通过热灭活野生型病毒体或与H2 TS 1突变体。这种现象似乎是腺病毒感染细胞内感染性病毒粒子胞质转运的细胞学标记。它可以通过实验与波形蛋白蛋白水解分离,发现波形蛋白蛋白水解具有血清型依赖性,仅发生在C亚组成员中,而与输入病毒的感染性无关。
Host cell interactions of human adenovirus serotypes belongng to subgroups B (adenovirus type 3 [Ad3] and Ad7) and C (Ad2 and Ad5) were comparatively analyzed at three levels: (i) binding of virus particles with host cell receptors; (ii) cointernalization of macromolecules with adenovirions; and (iii) adenovirus-induced cytoskeletal alterations. The association constants with human cell receptors were found to be similar to Ad2 and Ad3 (8 .times. 109 to 9 .times. 109 M-1), and the number of receptor sites per cell ranged from 5,000 (Ad2) to 7,000 (Ad3). Affinity blottings, competition experiments, and immunofluorescence stainings suggested that the receptor sites for adenovirus were distinct for members of subgroups B and C. Adenovirions increased the permeability of cells to macromolecules. We showed that this global effect could be divided into two distinct events: (i) cointernalization of macromolecules and virions into endocytotic vesicles, a phenomenon that occurred in a serotype-independent way, and (ii) release of macromolecules into the cytoplasm upon adenovirus-induced lysis of endosomal membranes. The latter process was found to be type specific and to require unaltered and infectious virus particles of serotype 2 or 5. Perinuclear condensation of the vimentin filament network was observed at early stages of infection with Ad2 or Ad5 but not with Ad3, Ad7, and noninfectious particles of Ad2 or Ad5, obtained by heat inactivation of wild-type virions or with the H2 ts1 mutant. This phenomenon appeared to be a cytological marker for cytoplasmic transit of infectious virions within adenovirus-infected cells. It could be experimentally dissociated from vimentin proteolysis, which was found to be serotype dependent, occurring only with members of subgroup C, regardless of the infectivity of the input virus.