Deletions within the 5′UTR of coxsackievirus B3:: Consequences for virus translation and replication
Deletions within the 5′UTR of coxsackievirus B3:: Consequences for virus translation and replication
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DOI：
10.1016/j.virol.2006.09.041
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发表时间：
2007-03-30
期刊：
影响因子：
3.7
通讯作者：
Whitton, J. Lindsay
中科院分区：
文献类型：
--
作者：
Hunziker, Isabelle P.;Cornell, Christopher T.;Whitton, J. Lindsay
针对柯萨奇病毒B3（CVB 3）的理想的基于RNA的疫苗的关键特征是（i）有限的基因组复制/病毒产生（以最小化疫苗相关的病理）和（ii）丰富的病毒蛋白合成（以最大化免疫原性）。这些属性可能适用于从其5'末端缺失多达250个核苷酸（m）的CVB 3 RNA;这些RNA不会产生感染性后代，但据报道它们保留了整个CVB 3 IRES（映射到与432-639相似的nt）并在转染细胞中产生大量病毒蛋白。在这里，我们构建了五个5' RNA缺失变体，令我们惊讶的是，它们未能保护免受CVB 3攻击。我们研究了这种失败的原因，并得出结论：（i）短至32 nt的5'端缺失消除了转染细胞中CVB 3 RNA的复制;（ii）这种缺失的RNA和其他具有较长缺失的RNA在转染细胞中不指导丰富的蛋白质合成，可能是它们复制能力丧失的结果;和（iii）CVB 3 IRES比以前认为的大得多，其5 ′边界位于残基76和125之间，非常接近脊髓灰质炎病毒IRES的边界。(c)2006年爱思唯尔公司All rights reserved.
Key features of an ideal RNA-based vaccine against coxsackievirus B3 (CVB3) are (i) limited genome replication/virus production (to minimize vaccine-related pathology) and (ii) abundant virus protein synthesis (to maximize immunogenicity). These attributes may apply to CVB3 RNAs lacking up to 250 nucleotides (m) from their 5' terminus; these RNAs do not give rise to infectious progeny, but they have been reported to retain the entire CVB3 IRES (mapped to nt similar to 432-639) and to produce large quantities of viral protein in transfected cells. Here, we constructed five 5' RNA deletion variants that, to our surprise, failed to protect against CVB3 challenge. We investigated the reasons for this failure and conclude that (i) a 5' terminal deletion as short as 32 nt abolishes CVB3 RNA replication in transfected cells; (ii) this deleted RNA, and others with longer deletions, do not direct abundant protein synthesis in transfected cells, probably as a consequence of their replicative incapacity; and (iii) the CVB3 IRES is substantially larger than previously thought, and its 5' boundary lies between residues 76 and 125, very closely approximating that of the poliovirus IRES. (c) 2006 Elsevier Inc. All rights reserved.