Blood clearance rates of adenovirus type 5 in mice

Blood clearance rates of adenovirus type 5 in mice
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DOI:
10.1099/0022-1317-81-11-2605
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发表时间:
2000-11-01
影响因子:
3.8
通讯作者:
Curiel, DT
Curiel, DT
中科院分区:
医学3区
文献类型:
--
作者:
Alemany, R;Suzuki, K;Curiel, DT

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5型腺病毒在血液中的持续存在与病毒感染的致病性以及该病毒在溶瘤和基因治疗中的应用有关。在本研究中,评价了小鼠血液中腺病毒清除的动力学。浓缩病毒单次接种到腔静脉后,病毒半衰期小于2分钟。枯否细胞(KC)耗竭导致病毒血症增加。尾静脉注射后,病毒和乳胶珠共定位在KIC内。KC清除的一个重要因素是颗粒的负电荷。删除六邻体高变区1的酸性延伸减少了病毒粒子的负电荷,但它没有增加血液持久性。用PEG(“PEG化”)包被降低了清除率,但也降低了感染性。
Persistence of adenovirus type 5 in blood has implications for the pathogenicity of the virus infection and for the use of this virus in oncolysis and gene therapy. In this study, the kinetics of adenovirus clearance from blood in mice has been evaluated. After a single inoculation of concentrated virus into the vena cava, virus half-life was less than 2 min. Depletion of Kupffer cells (KC) resulted in increased viraemia. After tail-vein injection, virus and latex beads co-localized within KIC. An important factor in clearance by KC is the negative charge of particles. Deletion of the hexon hypervariable region 1 acidic stretch decreased the negative charge of the virion but it did not increase blood persistence. Coating with PEG ('PEGylation') reduced the clearance rate but also reduced infectivity.