West Nile virus (WNV) genome RNAs with up to three adjacent mutations that disrupt long distance 5'-3' cyclization sequence basepairs are viable.
West Nile virus (WNV) genome RNAs with up to three adjacent mutations that disrupt long distance 5'-3' cyclization sequence basepairs are viable.
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DOI：
10.1016/j.virol.2011.01.008
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发表时间：
2011-03-30
期刊：
影响因子：
3.7
通讯作者：
Brinton MA
中科院分区：
文献类型：
--
作者：
Basu M;Brinton MA
蚊媒黄病毒基因组含有保守的5′和3′环化序列（CYC），可促进长距离RNA-RNA相互作用。在之前的研究中，黄病毒复制子RNA复制被单个或多个错配的CYC nt取代完全抑制。在本研究中，具有一个、两个或三个错配CYC取代的全长WNV基因组显示出降低的复制效率，但是是可行的，并且产生具有增加的复制效率的回复突变体。几个不同的三个相邻的错配CYC取代突变体RNA被第二个位点突变所拯救，该突变在5′-3′ CYC的内部基因组侧产生了额外的碱基对（nts 147-10913）。具有多达三个错配CYC突变的全长基因组是可行的并且可以通过单个nt自发突变来挽救的发现表明，需要多于三个相邻CYC碱基对取代以通过在基因组间重组体中产生错配来增加疫苗基因组的安全性。
Mosquito-borne flavivirus genomes contain conserved 5′ and 3′ cyclization sequences (CYC) that facilitate long distance RNA-RNA interactions. In previous studies, flavivirus replicon RNA replication was completely inhibited by single or multiple mismatching CYC nt substitutions. In the present study, full-length WNV genomes with one, two or three mismatching CYC substitutions showed reduced replication efficiencies but were viable and generated revertants with increased replication efficiency. Several different three adjacent mismatching CYC substitution mutant RNAs were rescued by a second site mutation that created an additional base pair (nts 147-10913) on the internal genomic side of the 5′-3′ CYC. The finding that full-length genomes with up to three mismatching CYC mutations are viable and can be rescued by a single nt spontaneous mutation indicates that more than three adjacent CYC basepair substitutions would be required to increase the safety of vaccine genomes by creating mismatches in inter-genomic recombinants.
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