Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage

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)

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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 Pondeville, Dr Emilie and McKimmie, Dr Clive and Pingen, Dr Marieke and Terry, Mrs Sandra and Lefteri, Dr Daniella and Shams, Dr Kave
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630008Arthropod-borne infections and emerging virus infections in high risk areas (Programme 4)Emma ThomsonMedical Research Council (MRC)MC_UU_12014/8III - Centre for Virus Research