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

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Autor/in:
Erscheinungsjahr:
2024
Medientyp:
Text
Schlagworte:
  • antiviral RNAi
  • arbovirus
  • Bunyaviricetes
  • Dcr2
  • mosquito
  • RVFV
Beschreibung:
  • 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 Bunyaviricetes, 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 Bunyaviricetes. For this, we used the Aedes aegypti-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 Bunyaviricetes: the Rift Valley fever virus (RVFV) vaccine strain MP12 (Phenuiviridae, Phlebovirus) and the Bunyamwera orthobunyavirus (BUNV; Peribunyaviridae, Orthobunyavirus). 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.

Lizenz:
  • info:eu-repo/semantics/openAccess
Quellsystem:
Forschungsinformationssystem der UHH

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