Integrative Analysis of Zika Virus Genome RNA Structure Reveals Critical Determinants of Viral Infectivity

doi:10.1016/j.chom.2018.10.011

. 2018 Dec 12;24(6):875-886.e5.

doi: 10.1016/j.chom.2018.10.011. Epub 2018 Nov 21.

Integrative Analysis of Zika Virus Genome RNA Structure Reveals Critical Determinants of Viral Infectivity

Pan Li¹, Yifan Wei¹, Miao Mei², Lei Tang¹, Lei Sun¹, Wenze Huang¹, Jianyu Zhou³, Chunlin Zou⁴, Shaojun Zhang¹, Cheng-Feng Qin⁵, Tao Jiang⁶, Jianfeng Dai⁴, Xu Tan⁷, Qiangfeng Cliff Zhang⁸

Affiliations

¹ MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
² School of Pharmaceutical Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.
³ Bioinformatics Division, BNRIST, Department of Computer Science and Technology, Tsinghua University, Beijing 100084, China.
⁴ Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China.
⁵ Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
⁶ Bioinformatics Division, BNRIST, Department of Computer Science and Technology, Tsinghua University, Beijing 100084, China; Department of Computer Science and Engineering, University of California, Riverside, CA 92521, USA.
⁷ School of Pharmaceutical Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Tsinghua-Peking Center for Life Sciences, Beijing 100084, China. Electronic address: xutan@tsinghua.edu.cn.
⁸ MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: qczhang@tsinghua.edu.cn.

PMID: 30472207
DOI: 10.1016/j.chom.2018.10.011

Free article

Integrative Analysis of Zika Virus Genome RNA Structure Reveals Critical Determinants of Viral Infectivity

Pan Li et al. Cell Host Microbe. 2018.

Free article

. 2018 Dec 12;24(6):875-886.e5.

doi: 10.1016/j.chom.2018.10.011. Epub 2018 Nov 21.

Authors

Affiliations

¹ MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
² School of Pharmaceutical Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.
³ Bioinformatics Division, BNRIST, Department of Computer Science and Technology, Tsinghua University, Beijing 100084, China.
⁴ Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China.
⁵ Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
⁶ Bioinformatics Division, BNRIST, Department of Computer Science and Technology, Tsinghua University, Beijing 100084, China; Department of Computer Science and Engineering, University of California, Riverside, CA 92521, USA.
⁷ School of Pharmaceutical Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Tsinghua-Peking Center for Life Sciences, Beijing 100084, China. Electronic address: xutan@tsinghua.edu.cn.
⁸ MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: qczhang@tsinghua.edu.cn.

PMID: 30472207
DOI: 10.1016/j.chom.2018.10.011

Abstract

Zika virus (ZIKV) strains can be classified into the ancestral African and contemporary Asian lineages, with the latter responsible for recent epidemics associated with neurological conditions. To understand how Asian strains lead to exacerbated disease, a crucial step is identifying genomic variations that affect infectivity and pathogenicity. Here we use two high-throughput sequencing approaches to assess RNA secondary structures and intramolecular RNA-RNA interactions in vivo for the RNA genomes of Asian and African ZIKV lineages. Our analysis identified functional RNA structural elements and a functional long-range intramolecular interaction specific for the Asian epidemic strains. Mutants that disrupt this extended RNA interaction between the 5' UTR and the E protein coding region reduce virus infectivity, which is partially rescued with compensatory mutants, restoring this RNA-RNA interaction. These findings illuminate the structural basis of ZIKV regulation and provide a resource for the discovery of RNA structural elements important for ZIKV infection.

Keywords: PARIS; RNA secondary structural element; RNA secondary structure; RNA structural domain; Zika virus; icSHAPE; long-range RNA-RNA interaction; viral RNA structural model.

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Integrative Analysis of Zika Virus Genome RNA Structure Reveals Critical Determinants of Viral Infectivity

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Integrative Analysis of Zika Virus Genome RNA Structure Reveals Critical Determinants of Viral Infectivity

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