Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells
Abstract Background Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. Results Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV)...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Genome Biology |
| Online Access: | https://doi.org/10.1186/s13059-023-03110-9 |
| _version_ | 1797397941209530368 |
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| author | Kuo-Chieh Liao Xuping Xie Anna Karin Beatrice Sundstrom Xin Ni Lim Kiat Kee Tan Yu Zhang Jing Zou Amanda Makha Bifani Hui Xian Poh Jia Jia Chen Wy Ching Ng Su Ying Lim Eng Eong Ooi October M. Sessions Yvonne Tay Pei-Yong Shi Roland G. Huber Yue Wan |
| author_facet | Kuo-Chieh Liao Xuping Xie Anna Karin Beatrice Sundstrom Xin Ni Lim Kiat Kee Tan Yu Zhang Jing Zou Amanda Makha Bifani Hui Xian Poh Jia Jia Chen Wy Ching Ng Su Ying Lim Eng Eong Ooi October M. Sessions Yvonne Tay Pei-Yong Shi Roland G. Huber Yue Wan |
| author_sort | Kuo-Chieh Liao |
| collection | DOAJ |
| description | Abstract Background Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. Results Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3′UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3′UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. Conclusions This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis. |
| first_indexed | 2024-03-09T01:17:27Z |
| format | Article |
| id | doaj.art-47da49f037b74b8e94d5fc3d0069ec9f |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-03-09T01:17:27Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-47da49f037b74b8e94d5fc3d0069ec9f2023-12-10T12:20:51ZengBMCGenome Biology1474-760X2023-12-0124111710.1186/s13059-023-03110-9Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cellsKuo-Chieh Liao0Xuping Xie1Anna Karin Beatrice Sundstrom2Xin Ni Lim3Kiat Kee Tan4Yu Zhang5Jing Zou6Amanda Makha Bifani7Hui Xian Poh8Jia Jia Chen9Wy Ching Ng10Su Ying Lim11Eng Eong Ooi12October M. Sessions13Yvonne Tay14Pei-Yong Shi15Roland G. Huber16Yue Wan17Stem Cell and Regenerative Biology, Genome Institute of SingaporeDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical SchoolStem Cell and Regenerative Biology, Genome Institute of SingaporeStem Cell and Regenerative Biology, Genome Institute of SingaporeStem Cell and Regenerative Biology, Genome Institute of SingaporeDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical SchoolStem Cell and Regenerative Biology, Genome Institute of SingaporeCancer Science Institute of Singapore, National University of SingaporeProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical SchoolStem Cell and Regenerative Biology, Genome Institute of SingaporeProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical SchoolSaw Swee Hock School of Public Health, National University of SingaporeCancer Science Institute of Singapore, National University of SingaporeDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchBiomolecular Function Discovery, Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR)Stem Cell and Regenerative Biology, Genome Institute of SingaporeAbstract Background Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. Results Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3′UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3′UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. Conclusions This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis.https://doi.org/10.1186/s13059-023-03110-9 |
| spellingShingle | Kuo-Chieh Liao Xuping Xie Anna Karin Beatrice Sundstrom Xin Ni Lim Kiat Kee Tan Yu Zhang Jing Zou Amanda Makha Bifani Hui Xian Poh Jia Jia Chen Wy Ching Ng Su Ying Lim Eng Eong Ooi October M. Sessions Yvonne Tay Pei-Yong Shi Roland G. Huber Yue Wan Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells Genome Biology |
| title | Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells |
| title_full | Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells |
| title_fullStr | Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells |
| title_full_unstemmed | Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells |
| title_short | Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells |
| title_sort | dengue and zika rna rna interactomes reveal pro and anti viral rna in human cells |
| url | https://doi.org/10.1186/s13059-023-03110-9 |
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