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Zika virus noncoding RNA suppresses apoptosis and is required for virus transmission by mosquitoes

Author

Listed:
  • Andrii Slonchak

    (The University of Queensland)

  • Leon E. Hugo

    (QIMR Berghofer Medical Research Institute)

  • Morgan E. Freney

    (The University of Queensland)

  • Sonja Hall-Mendelin

    (Public Health Virology, Forensic and Scientific Services, Department of Health, Queensland Government)

  • Alberto A. Amarilla

    (The University of Queensland)

  • Francisco J. Torres

    (The University of Queensland)

  • Yin Xiang Setoh

    (The University of Queensland)

  • Nias Y. G. Peng

    (The University of Queensland)

  • Julian D. J. Sng

    (The University of Queensland)

  • Roy A. Hall

    (The University of Queensland)

  • Andrew F. van den Hurk

    (Public Health Virology, Forensic and Scientific Services, Department of Health, Queensland Government)

  • Gregor J. Devine

    (QIMR Berghofer Medical Research Institute)

  • Alexander A. Khromykh

    (The University of Queensland)

Abstract

Flaviviruses, including Zika virus (ZIKV), utilise host mRNA degradation machinery to produce subgenomic flaviviral RNA (sfRNA). In mammalian hosts, this noncoding RNA facilitates replication and pathogenesis of flaviviruses by inhibiting IFN-signalling, whereas the function of sfRNA in mosquitoes remains largely elusive. Herein, we conduct a series of in vitro and in vivo experiments to define the role of ZIKV sfRNA in infected Aedes aegypti employing viruses deficient in production of sfRNA. We show that sfRNA-deficient viruses have reduced ability to disseminate and reach saliva, thus implicating the role for sfRNA in productive infection and transmission. We also demonstrate that production of sfRNA alters the expression of mosquito genes related to cell death pathways, and prevents apoptosis in mosquito tissues. Inhibition of apoptosis restored replication and transmission of sfRNA-deficient mutants. Hence, we propose anti-apoptotic activity of sfRNA as the mechanism defining its role in ZIKV transmission.

Suggested Citation

  • Andrii Slonchak & Leon E. Hugo & Morgan E. Freney & Sonja Hall-Mendelin & Alberto A. Amarilla & Francisco J. Torres & Yin Xiang Setoh & Nias Y. G. Peng & Julian D. J. Sng & Roy A. Hall & Andrew F. van, 2020. "Zika virus noncoding RNA suppresses apoptosis and is required for virus transmission by mosquitoes," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16086-y
    DOI: 10.1038/s41467-020-16086-y
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    Cited by:

    1. Andrii Slonchak & Rhys Parry & Brody Pullinger & Julian D. J. Sng & Xiaohui Wang & Teresa F. Buck & Francisco J. Torres & Jessica J. Harrison & Agathe M. G. Colmant & Jody Hobson-Peters & Roy A. Hall , 2022. "Structural analysis of 3’UTRs in insect flaviviruses reveals novel determinants of sfRNA biogenesis and provides new insights into flavivirus evolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Xiang Chen & Yan Wang & Zhonghe Xu & Meng-Li Cheng & Qing-Qing Ma & Rui-Ting Li & Zheng-Jian Wang & Hui Zhao & Xiaobing Zuo & Xiao-Feng Li & Xianyang Fang & Cheng-Feng Qin, 2023. "Zika virus RNA structure controls its unique neurotropism by bipartite binding to Musashi-1," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Xiaolin Niu & Ruirui Sun & Zhifeng Chen & Yirong Yao & Xiaobing Zuo & Chunlai Chen & Xianyang Fang, 2021. "Pseudoknot length modulates the folding, conformational dynamics, and robustness of Xrn1 resistance of flaviviral xrRNAs," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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