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Dengue and Zika RNA-RNA Interactomes Reveal Virus Permissive and Restrictive Factors in Human Cells

33 Pages Posted: 2 Jul 2021 Publication Status: Review Complete

See all articles by Xin Ni Lim

Xin Ni Lim

Genome Institute of Singapore - Stem Cell and Regenerative Biology

Xuping Xie

University of Texas Medical Branch-Galveston - Department of Biochemistry and Molecular Biology

Anna Karin Beatrice Sundstrom

Duke-NUS Graduate Medical School - Program in Emerging Infectious Diseases

Kiat Yee Tan

Genome Institute of Singapore - Stem Cell and Regenerative Biology

Jing Zou

University of Texas Medical Branch-Galveston - Department of Biochemistry and Molecular Biology

Amanda Makha Bifani

Duke-NUS Graduate Medical School - Program in Emerging Infectious Diseases

Kuo Chieh Liao

Genome Institute of Singapore - Stem Cell and Regenerative Biology

Hui Xian Poh

Genome Institute of Singapore - Stem Cell and Regenerative Biology

Jia Jia Chan

National University of Singapore (NUS) - Cancer Science Institute of Singapore

Wy Ching Ng

Duke-NUS Graduate Medical School - Program in Emerging Infectious Diseases

Su Ying Lim

Genome Institute of Singapore - Stem Cell and Regenerative Biology

Eng Eong Ooi

Duke-NUS Graduate Medical School - Programme in Emerging Infectious Diseases

October Sessions

National University of Singapore (NUS) - Saw Swee Hock School of Public Health

Yvonne Tay

National University of Singapore (NUS) - Cancer Science Institute of Singapore

Pei-Yong Shi

University of Texas Medical Branch-Galveston - Department of Biochemistry and Molecular Biology

Roland G. Huber

Agency for Science, Technology and Research (A*STAR) - Biomolecular Function Discovery

Yue Wan

Genome Institute of Singapore - Stem Cell and Regenerative Biology

More...

Abstract

Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. Here, we used 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 found 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 and the binding is primarily driven by hybridization energetics. We observed that virus interacting host RNAs tend to be downregulated upon virus infection and identified a conserved set of virus responders that binds to most DENV and ZIKV. Knockdown of several short non-coding RNAs, including miR19a-3p, SCARNA2 and 7SK RNA resulted in a decrease in virus growth, 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. This study demonstrates that host RNAs in themselves can impact virus growth in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during virus pathogenesis.

Suggested Citation

Lim, Xin Ni and Xie, Xuping and Sundstrom, Anna Karin Beatrice and Tan, Kiat Yee and Zou, Jing and Bifani, Amanda Makha and Liao, Kuo Chieh and Poh, Hui Xian and Chan, Jia Jia and Ng, Wy Ching and Lim, Su Ying and Ooi, Eng Eong and Sessions, October and Tay, Yvonne and Shi, Pei-Yong and Huber, Roland G. and Wan, Yue, Dengue and Zika RNA-RNA Interactomes Reveal Virus Permissive and Restrictive Factors in Human Cells. Available at SSRN: https://ssrn.com/abstract=3879086 or http://dx.doi.org/10.2139/ssrn.3879086
This version of the paper has not been formally peer reviewed.

Xin Ni Lim

Genome Institute of Singapore - Stem Cell and Regenerative Biology

60 Biopolis St
138672
Singapore

Xuping Xie

University of Texas Medical Branch-Galveston - Department of Biochemistry and Molecular Biology ( email )

Galveston, TX 77555
United States

Anna Karin Beatrice Sundstrom

Duke-NUS Graduate Medical School - Program in Emerging Infectious Diseases ( email )

8 College Road
Singapore

Kiat Yee Tan

Genome Institute of Singapore - Stem Cell and Regenerative Biology

60 Biopolis St
138672
Singapore

Jing Zou

University of Texas Medical Branch-Galveston - Department of Biochemistry and Molecular Biology ( email )

Galveston, TX 77555
United States

Amanda Makha Bifani

Duke-NUS Graduate Medical School - Program in Emerging Infectious Diseases ( email )

8 College Road
Singapore

Kuo Chieh Liao

Genome Institute of Singapore - Stem Cell and Regenerative Biology

60 Biopolis St
138672
Singapore

Hui Xian Poh

Genome Institute of Singapore - Stem Cell and Regenerative Biology

60 Biopolis St
138672
Singapore

Jia Jia Chan

National University of Singapore (NUS) - Cancer Science Institute of Singapore

Singapore

Wy Ching Ng

Duke-NUS Graduate Medical School - Program in Emerging Infectious Diseases ( email )

8 College Road
Singapore

Su Ying Lim

Genome Institute of Singapore - Stem Cell and Regenerative Biology

60 Biopolis St
138672
Singapore

Eng Eong Ooi

Duke-NUS Graduate Medical School - Programme in Emerging Infectious Diseases ( email )

Singapore

October Sessions

National University of Singapore (NUS) - Saw Swee Hock School of Public Health ( email )

16 Medical Drive
#10-01
117597
Singapore

Yvonne Tay

National University of Singapore (NUS) - Cancer Science Institute of Singapore

Singapore

Pei-Yong Shi

University of Texas Medical Branch-Galveston - Department of Biochemistry and Molecular Biology ( email )

Galveston, TX 77555
United States

Roland G. Huber

Agency for Science, Technology and Research (A*STAR) - Biomolecular Function Discovery

30 Biopolis Street
#07-01 Matrix
Singapore, 138671
China

Yue Wan (Contact Author)

Genome Institute of Singapore - Stem Cell and Regenerative Biology ( email )

60 Biopolis Street
138672
Singapore

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