Lefteri, D. A. et al. (2022) Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage. Proceedings of the National Academy of Sciences of the United States of America, 119(24), e211430911. (doi: 10.1073/pnas.2114309119) (PMID:35675424) (PMCID:PMC9214539)
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Abstract
Viruses transmitted by Aedes mosquitoes are an increasingly important global cause of disease. Defining common determinants of host susceptibility to this large group of heterogenous pathogens is key for informing the rational design of panviral medicines. Infection of the vertebrate host with these viruses is enhanced by mosquito saliva, a complex mixture of salivary-gland-derived factors and microbiota. We show that the enhancement of infection by saliva was dependent on vascular function and was independent of most antisaliva immune responses, including salivary microbiota. Instead, the Aedes gene product sialokinin mediated the enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having a vertebrate-like tachykinin sequence and is absent from Anopheles mosquitoes, which are incompetent for most arthropod-borne viruses, whose saliva was not proviral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have the potential to limit disease severity following infection with Aedes-mosquito-borne viruses.
| Item Type: | Articles |
|---|---|
| Additional Information: | RMW was supported by Swiss National Science Foundation grant PP00P3_170664. VM and PC were supported by Research England QR-GCRF funds 2021 allocation. CSM was supported by a Wellcome Trust Seed award in Science (108227/Z/15/Z ), a Royal Society Research grant (RGS\R1\191390 ) and a University of Leeds University Academic Fellowship. EP was supported by the UK Medical Research Council (MC_UU_12014.8) to EP. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Bryden, Dr Steven and Varjak, Dr Margus and McKimmie, Dr Clive and Pondeville, Dr Emilie and Pingen, Dr Marieke and Terry, Mrs Sandra and Shams, Dr Kave and Lefteri, Dr Daniella |
| Authors: | Lefteri, D. A., Bryden, S. R., Pingen, M., Terry, S., McCafferty, A., Beswick, E. F., Georgiev, G., Van der Laan, M., Mastrullo, V., Campagnolo, P., Waterhouse, R. M., Varjak, M., Merits, A., Fragkoudis, R., Griffin, S., Shams, K., Pondeville, E., and McKimmie, C. S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 08 June 2022 |
| Copyright Holders: | Copyright © The Author(s) 2022 |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 119(24): e211430911 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
| Data DOI: | 10.5518/1163 |
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