Spindle-E Acts Antivirally Against Alphaviruses in Mosquito Cells

Mosquitoes transmit several human- and animal-pathogenic alphaviruses (Togaviridae family). In alphavirus-infected mosquito cells two different types of virus-specific small RNAs are produced as part of the RNA interference response: short-interfering (si)RNAs and PIWI-interacting (pi)RNAs. The siRN...

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Vydáno v:Viruses Ročník 10; číslo 2; s. 88
Hlavní autoři: Varjak, Margus, Dietrich, Isabelle, Sreenu, Vattipally B., Till, Bethan Eluned, Merits, Andres, Kohl, Alain, Schnettler, Esther
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI AG 18.02.2018
MDPI
Témata:
Ae. aegypti
Aedes aegypti
Alphavirus
Alphavirus Infections - virology
Animals
Antiviral activity
Antiviral drugs
antiviral responses
Argonaute 2 protein
Cells, Cultured
Culicidae - virology
DNA helicase
Insect Proteins - genetics
Mosquitoes
Replication
RNA Interference
RNA, Small Untranslated - genetics
RNA-mediated interference
siRNA
Virus Replication
antiviral responses
RNA interference
alphavirus
Ae. aegypti
ISSN:1999-4915, 1999-4915
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Shrnutí:Mosquitoes transmit several human- and animal-pathogenic alphaviruses (Togaviridae family). In alphavirus-infected mosquito cells two different types of virus-specific small RNAs are produced as part of the RNA interference response: short-interfering (si)RNAs and PIWI-interacting (pi)RNAs. The siRNA pathway is generally thought to be the main antiviral pathway. Although an antiviral activity has been suggested for the piRNA pathway its role in host defences is not clear. Knock down of key proteins of the piRNA pathway (Ago3 and Piwi5) in Aedes aegypti-derived cells reduced the production of alphavirus chikungunya virus (CHIKV)-specific piRNAs but had no effect on virus replication. In contrast, knock down of the siRNA pathway key protein Ago2 resulted in an increase in virus replication. Similar results were obtained when expression of Piwi4 was silenced. Knock down of the helicase Spindle-E (SpnE), an essential co-factor of the piRNA pathway in Drosophila melanogaster, resulted in increased virus replication indicating that SpnE acts as an antiviral against alphaviruses such as CHIKV and the related Semliki Forest virus (SFV). Surprisingly, this effect was found to be independent of the siRNA and piRNA pathways in Ae. aegypti cells and specific for alphaviruses. This suggests a small RNA-independent antiviral function for this protein in mosquitoes.
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Present address: Experimental Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK.
ISSN:1999-4915
1999-4915
DOI:10.3390/v10020088