In Vitro Evolution of Bovine Foamy Virus Variants with Enhanced Cell-Free Virus Titers and Transmission.

In Vitro Evolution of Bovine Foamy Virus Variants with Enhanced Cell-Free Virus Titers and Transmission.
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DOI:
10.3390/v7112907
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发表时间:
2015-11-11
期刊:
Viruses
影响因子:
--
通讯作者:
Löchelt M
Löchelt M
中科院分区:
其他
文献类型:
--
作者:
Bao Q;Hipp M;Hugo A;Lei J;Liu Y;Kehl T;Hechler T;Löchelt M

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病毒传播对于传播病毒感染是必不可少的,并且是通过无细胞传播或细胞-细胞接触发生的高度协调的过程。牛泡沫病毒(BFV)的传播是高度细胞相关的,与不可检测的无细胞传播。然而,BFV颗粒出芽可以通过野生型(wt)BFV Gag和Env的过表达或通过豆蔻酰化膜靶向信号将Gag人工重靶向质膜来诱导,与其他泡沫病毒中的观察结果非常相似。因此,野生型BFV的颗粒释放机制似乎是通过体外选择和进化来研究病毒适应无细胞传播的优良模型系统。使用对牛和非牛细胞中具有高无细胞感染性的BFV变体的选择,在两种细胞类型中,感染性从几乎没有感染单位急剧增加到约105-106 FFU(荧光病灶形成单位)/mL。重要的是,所选的具有高滴度(HT)无细胞感染性的BFV变体仍然可以通过细胞-细胞接触传播,并被自然感染奶牛的血清中和。这些选定的HT-BFV变体将揭示病毒传播和病毒感染传播的潜在干预途径。它还将有助于改进或发展新的有希望的抗逆转录病毒疗法方法。
Virus transmission is essential for spreading viral infections and is a highly coordinated process which occurs by cell-free transmission or cell–cell contact. The transmission of Bovine Foamy Virus (BFV) is highly cell-associated, with undetectable cell-free transmission. However, BFV particle budding can be induced by overexpression of wild-type (wt) BFV Gag and Env or artificial retargeting of Gag to the plasma membrane via myristoylation membrane targeting signals, closely resembling observations in other foamy viruses. Thus, the particle release machinery of wt BFV appears to be an excellent model system to study viral adaption to cell-free transmission by in vitro selection and evolution. Using selection for BFV variants with high cell-free infectivity in bovine and non-bovine cells, infectivity dramatically increased from almost no infectious units to about 105–106 FFU (fluorescent focus forming units)/mL in both cell types. Importantly, the selected BFV variants with high titer (HT) cell-free infectivity could still transmit via cell-cell contacts and were neutralized by serum from naturally infected cows. These selected HT–BFV variants will shed light into virus transmission and potential routes of intervention in the spread of viral infections. It will also allow the improvement or development of new promising approaches for antiretroviral therapies.
DOI: 10.1371/journal.pone.0031108
发表时间: 2012
期刊: PloS one
影响因子: 3.7
作者:
Tobaly-Tapiero J;Zamborlini A;Bittoun P;Saïb A
通讯作者: Saïb A