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The microvascular capillaries and post-capillary venules affected during orthoflavivirus-related haemorrhagic disease consist of an endothelial cell (EC) barrier ensheathed in and supported by perivascular cells (pericytes), and we recently identified a critical role for pericytes in amplifying dengue microvascular dysfunction. The orthoflavivirus non-structural protein 1 (NS1) has been implicated in endothelial dysfunction and vascular leakage for several tick- and mosquito-borne flaviviruses. Here, we examined whether NS1 from AHFV and KFDV disrupts microvascular barrier integrity in pericyte\u2013EC cocultures. We found AHFV and KFDV NS1 to disrupt the ability of pericytes to support EC function, which is required for maintenance of the microvascular barrier. However, under our experimental conditions, we detected no endothelial hyperpermeability upon NS1 treatment in ECs cultured alone or in combination with pericytes. Our findings suggest that the concomitant impairment of both EC and pericyte function may be required for NS1 to induce microvascular hyperpermeability. Our work highlights the potentially synergistic effects of microvascular cells during orthoflavivirus haemorrhage and emphasizes the need for further work into the mechanisms of vascular dysfunction during AHFV and KFDV infection.<\/jats:p>","DOI":"10.1099\/jgv.0.002325","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:16:21Z","timestamp":1787847381000},"source":"Crossref","is-referenced-by-count":0,"title":["Pericyte dysfunction alone may be insufficient to drive tick-borne orthoflavivirus non-structural protein 1-mediated microvascular permeability"],"prefix":"10.1099","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1751-9592","authenticated-orcid":false,"given":"Emma","family":"Brown","sequence":"first","affiliation":[{"name":"School of Biosciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK"},{"name":"The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-3392","authenticated-orcid":false,"given":"Justin","family":"Duruanyanwu","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK"},{"name":"The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8957-3969","authenticated-orcid":false,"given":"Paola","family":"Campagnolo","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0977-8807","authenticated-orcid":false,"given":"Kevin","family":"Maringer","sequence":"additional","affiliation":[{"name":"The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0714-0"},{"key":"R2","article-title":"Statistical Yearbook 2023","year":"2023"},{"key":"R3","first-page":"314","article-title":"Current status of alkhurma hemorrhagic fever virus infection: future concerns and considerations","volume":"47","author":"Aljuaid","year":"2024","journal-title":"New Microbiol"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/s0035-9203(97)90215-7"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1186\/s12982-025-00518-5"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.3201\/eid1612.100417"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2004.11.012"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2010.09.032"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00258-20"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00844-21"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.3390\/v17070923"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2020.06.011"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa3787"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007033"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005738"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006673"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12748"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2014.01.011"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001634"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.3390\/v4113209"},{"key":"R21","doi-asserted-by":"crossref","first-page":"D678","DOI":"10.1093\/nar\/gkac1003","article-title":"Introducing the bacterial and viral bioinformatics resource center (BV-BRC): a resource combining PATRIC, IRD and ViPR","volume":"51","author":"Olson","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msae263"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.22.4673"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1205002"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67289-8"},{"key":"R27","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis. 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