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Virology. 2018 Nov;524:114-126. doi: 10.1016/j.virol.2018.08.018. Epub 2018 Aug 30.

Homologous RNA secondary structure duplications in 3' untranslated region influence subgenomic RNA production and replication of dengue virus.

Author information

1
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
2
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
3
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. Electronic address: hanxia@wh.iov.cn.
4
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. Electronic address: yzm@wh.iov.cn.

Abstract

Subgenomic flavivirus RNA (sfRNA) is essential for flavivirus-induced cytopathicity. sfRNA-deficient mutant dengue virus (DENV) M8 harboring a deleted domain II in the 3' untranslated region (UTR) has severely decreased cytopathicity and replication efficiency. Here, recovered viruses acquired from M8 by serial passages replicated similarly to the wild type (WT) but produced two types of sfRNA, whereas only one was detected in WT infected cells, resulting in mildly decreased cytopathicity. Sequencing and structure prediction showed that recovered viruses acquired a novel additional partial domain I sequence duplication and formed analogous RNA secondary structures. This was the first experimental evidence verifying that a longer precursor may exist in the 3' UTR of DENV. Additionally, the duplicated structures could be compensated by the homologous structures from other flaviviruses, rather than heterologous viruses, implying that homologous secondary structures or higher tertiary structures played more important roles in sfRNA production and viral replication.

KEYWORDS:

3′ untranslated region; Dengue virus; RNA secondary structure duplication; Replication; Subgenomic flavivirus RNA

PMID:
30172996
DOI:
10.1016/j.virol.2018.08.018
[Indexed for MEDLINE]

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