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Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness.

  • Manokaran G Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore. Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Finol E Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Swiss Tropical and Public Health Institute, Universität Basel, Switzerland.
  • Wang C Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA.
  • Gunaratne J Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Institute of Molecular and Cell Biology, Singapore.
  • Bahl J Center for Infectious Diseases, The University of Texas School of Public Health, Houston, TX, USA.
  • Ong EZ Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore.
  • Tan HC Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore.
  • Sessions OM Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore.
  • Ward AM Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore.
  • Gubler DJ Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore.
  • Harris E Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA.
  • Garcia-Blanco MA Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA. Department of Molecular Genetics and Microbiology and Center for RNA Biology, Duke University, Durham, NC, USA.
  • Ooi EE Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Singapore-Massachusetts Institute of Technology Alliance in Research and Technology Infectious Disease Interdisciplinary Research Group, Singapore. engeong.ooi@duke-nus.edu.sg.
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  • 2015-07-04
Published in:
  • Science (New York, N.Y.). - 2015
Animals
Biodiversity
Chlorocebus aethiops
DEAD Box Protein 58
DEAD-box RNA Helicases
Dengue
Dengue Virus
Humans
Immunity, Innate
Interferon Type I
Puerto Rico
RNA, Viral
Transcription Factors
Tripartite Motif Proteins
Ubiquitin-Protein Ligases
Ubiquitination
Vero Cells
Virus Replication
English The global spread of dengue virus (DENV) infections has increased viral genetic diversity, some of which appears associated with greater epidemic potential. The mechanisms governing viral fitness in epidemiological settings, however, remain poorly defined. We identified a determinant of fitness in a foreign dominant (PR-2B) DENV serotype 2 (DENV-2) clade, which emerged during the 1994 epidemic in Puerto Rico and replaced an endemic (PR-1) DENV-2 clade. The PR-2B DENV-2 produced increased levels of subgenomic flavivirus RNA (sfRNA) relative to genomic RNA during replication. PR-2B sfRNA showed sequence-dependent binding to and prevention of tripartite motif 25 (TRIM25) deubiquitylation, which is critical for sustained and amplified retinoic acid-inducible gene 1 (RIG-I)-induced type I interferon expression. Our findings demonstrate a distinctive viral RNA-host protein interaction to evade the innate immune response for increased epidemiological fitness.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/232221
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