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Dummunee, Krittika, Parry, Rhys, Redecke, Lars, Varjak, Margus, Brennan, Benjamin, Kohl, Alain and McFarlane, Melanie (2025) 'The catalytic tetrad of Aedes aegypti Argonaute 2 is critical for the antiviral activity of the exogenous siRNA pathway'. Journal of Biological Chemistry, p. 108332. (In Press)
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Abstract
Viruses transmitted by biting arthropods, arboviruses, pose a significant global health and economic threat. Climate change is exacerbating this issue by expanding the range of disease-carrying vectors. Effective control of arbovirus transmission often relies on targeting the vectors, making it crucial to understand the interactions between the virus and its vector. The exogenous siRNA (exo-siRNA) pathway is a key antiviral defence mechanism in mosquitoes such as Aedes aegypti. Argonaute 2 (Ago2) is a central protein in this pathway, responsible for antiviral activity. While the PIWI domain of Ago proteins is known to mediate slicing activity, not all Ago proteins possess this slicing function. To understand the antiviral mechanism of Ago2 in Ae. aegypti, we aimed to confirm the presence of the catalytic tetrad, a group of amino acids known to be crucial for slicing activity. Here, we confirmed the tetrad (D740, E780, D812, and H950) in Ae. aegypti Ago2 and demonstrated its essential role in antiviral and siRNA pathway activity. Our findings show that the catalytic tetrad is necessary for the degradation of siRNA passenger strands. When the tetrad is absent, siRNA duplexes accumulate, leading to a loss of siRNA pathway function. This underscores the critical role of the tetrad in the antiviral defence mechanism of Ae. aegypti.
| Item Type: | Article |
|---|---|
| Subjects: | QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control |
| Faculty: Department: | Biological Sciences > Department of Tropical Disease Biology |
| Digital Object Identifer (DOI): | https://doi.org/10.1016/j.jbc.2025.108332 |
| Depositing User: | Rachael Kedge |
| Date Deposited: | 25 Feb 2025 14:38 |
| Last Modified: | 25 Feb 2025 14:38 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/26240 |
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