@article{50df971e6279438eb262d378391442fb,
title = "Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage",
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 het-erogenous 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.",
keywords = "mosquitoes, arbovirus, inflammation, endothelium",
author = "Lefteri, {Daniella A.} and Bryden, {Steven R.} and Marieke Pingen and Sandra Terry and Ailish McCafferty and Beswick, {Emily F.} and Georgi Georgiev and {Van der Laan}, Marleen and Valeria Mastrullo and Paola Campagnolo and Waterhouse, {Robert M.} and Margus Varjak and Andres Merits and Rennos Fragkoudis and Stephen Griffin and Kave Shams and Emilie Pondeville and McKimmie, {Clive S.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Kamila Fras and Kirby Brown, undergraduate students at the University of Glasgow, and David Kerrigan (Medical Research Council [MRC]-University of Glasgow Centre for Virus Research) who helped with salivation of mosquitoes. Mosquito colonies were kindly supplied by E. Devaney, University of Glasgow, United Kingdom (Ae. aegypti); Dr. A.-B. Failloux, Institut Pasteur, France (Ae. albopictus La Providence INFRAVEC2 line); Dr. M. Weill, Uni-versit{\'e}de Montpellier, France (Cx. pipiens quinquefasciatus SLAB strain); Dr. Francesco Baldini and Dorothy Armstrong, University of Glasgow (An. gambiae Kisumu strain); and Dr. C. Bourgouin, Institut Pasteur, France (An. coluzzii Ngousso strain, referred to as An. gambiae in this report, and An. stephensi Sda 500 strain). We also kindly thank Dr. Kevin Mariner (Pirbright Institute, United Kingdom) for his detailed discussions and preliminary analysis of Aedes salivary gene transcripts; Yonca Keskek Turk for supplying the plaque assay picture of SFV; the University of Leeds Faculty of Medicine & Health Flow Cytometry and Imaging Facilities; the University of Leeds for funding D.A.L.; the University of Leeds St James{\textquoteright} Biomedical Services and Gillian Cardwell for assistance with mouse studies. R.M.W. was supported by Swiss National Science Foundation Grant PP00P3_170664. V.M. and P.C. were supported by Research England QR-GCRF funds 2021 allocation. C.S.M. 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. E.P. was supported by the UK MRC (MC_UU_12014/8). M.P. was supported by the UK MRC (MR/M019764/1 and MRV0109721). This research was funded in whole or in part by the Wellcome Trust. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript (AAM) version arising from this submission. Publisher Copyright: {\textcopyright} 2022 National Academy of Sciences. All rights reserved.",
year = "2022",
month = jun,
day = "14",
doi = "10.1073/pnas.2114309119",
language = "English",
volume = "119",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "24",
}