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

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 den Hurk, Gregor J. Devine and Alexander A. Khromykh ()
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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

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16086-y

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