| Autor: |
Varjak M; MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK., Gestuveo RJ; MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.; Division of Biological Sciences, College of Arts and Sciences, University of the Philippines Visayas, Miagao, Iloilo 5023, Philippines., Burchmore R; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK., Schnettler E; Bernhard-Nocht-Institut for Tropical Medicine, 20359 Hamburg, Germany.; German Centre for Infection Research (DZIF), partner site Hamburg-Luebeck-Borstel-Riems, 20359 Hamburg, Germany.; Faculty of Mathematics, Informatics and Natural Sciences, University Hamburg, 20148 Hamburg, Germany., Kohl A; MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK. |
| Abstrakt: |
Mosquitoes, such as Aedes aegypti , can transmit arboviruses to humans. The exogenous short interfering RNA (exo-siRNA) pathway plays a major antiviral role in controlling virus infection in mosquito cells. The Dicer 2 (Dcr2) nuclease is a key effector protein in this pathway, which cleaves viral double-stranded RNA into virus-derived siRNAs that are further loaded onto an effector called Argonaute 2 (Ago2), which as part of the multiprotein RNA-induced silencing complex (RISC) targets and cleaves viral RNA. In order to better understand the effector protein Dcr2, proteomics experiments were conducted to identify interacting cellular partners. We identified several known interacting partners including Ago2, as well as two novel and previously uncharacterized Ae. aegypti proteins. The role of these two proteins was further investigated, and their interactions with Dcr2 verified by co-immunoprecipitation. Interestingly, despite their ability to interact with Ago2 and Piwi4, neither of these proteins was found to affect exo-siRNA silencing in a reporter assay. However, one of these proteins, Q0IFK9, subsequently called aBravo ( a edine br oadly active a nti v iral pr o tein), was found to mediate antiviral activity against positive strand RNA arboviruses. Intriguingly the presence of Dcr2 was not necessary for this effect, suggesting that this interacting antiviral effector may act as part of protein complexes with potentially separate antiviral activities. |
