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Volume 105, Issue 11

Dicer-2 mutations in cells lead to a diminished antiviral function against Rift Valley fever virus and Bunyamwera virus infection Open Access

Abstract

Mosquitoes are known to transmit different arthropod-borne viruses belonging to various virus families. The exogenous small interfering RNA pathway plays an important role in the mosquito defence against such virus infections, with Dicer-2 (Dcr2) as one of the key proteins that initiates the cleavage of viral dsRNAs into 21 nt long virus-derived small interfering RNAs. Previous data identified the importance of various motifs in Dcr2 for its small interfering RNA (siRNA)-mediated antiviral activity. However, all these data focus on positive-strand RNA viruses, although negative-strand RNA viruses, like , include several important mosquito-borne viruses. Here, we aim to investigate the importance of different domains of Dcr2 for antiviral activity against viruses of the . For this, we used the derived Dcr2 knock-out cell line Aag2-AF319 to study the importance of the helicase, RNase III and PIWI–Argonaute–Zwille domains of Dcr2 on the antiviral activity of two viruses belonging to different families of the : the Rift Valley fever virus (RVFV) vaccine strain MP12 (, ) and the Bunyamwera orthobunyavirus (BUNV; , ). All three domains were determined to be critical for the antiviral activity against both RVFV and BUNV. Interestingly, one specific mutation in the helicase domain (KN) did not result in a loss of antiviral activity for RVFV, but for BUNV, despite losing the ability to produce 21 nt siRNAs.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antiviral RNAi , arbovirus , Bunyaviricetes , Dcr2 , mosquito and RVFV
Funding
This study was supported by the:
  • Deutsche Forschungsgemeinschaft (Award BE 5748/1-2, STE 1428/5-2, 398066876/GRK 2485/1)
    • Principle Award Recipient: SusannDornbusch
  • Deutsche Forschungsgemeinschaft (Award 497659464)
    • Principle Award Recipient: MelindaReuter
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2024-11-07
2024-12-02
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Dicer-2 mutations in Aedes aegypti cells lead to a diminished antiviral function against Rift Valley fever virus and Bunyamwera virus infection
J. Gen. Virol. 105, 002046 (2024); https://doi.org/10.1099/jgv.0.002046
/content/journal/jgv/10.1099/jgv.0.002046
/content/journal/jgv/10.1099/jgv.0.002046
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