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Lefteri, DA orcid.org/0000-0002-9985-4254, Bryden, SR orcid.org/0000-0001-5408-6047, Pingen, M orcid.org/0000-0001-5689-9076 et al. (15 more authors) (2022) Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage. Proceedings of the National Academy of Sciences (PNAS), 119 (24). e2114309119. ISSN 0027-8424
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). |
Keywords: | Mosquitoes; arbovirus; inflammation; endothelium |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 108227/B/15/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Apr 2022 09:58 |
Last Modified: | 15 Jan 2025 14:07 |
Status: | Published |
Publisher: | National Academy of Sciences |
Identification Number: | 10.1073/pnas.2114309119 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:185862 |
Available Versions of this Item
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Mosquito saliva sialokinin-dependent enhancement of arbovirus infection through endothelial barrier leakage. (deposited 21 Dec 2023 14:17)
- Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage. (deposited 21 Apr 2022 09:58) [Currently Displayed]
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