{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:54:29Z","timestamp":1790794469376,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014645","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000}}],"reference-count":105,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210462\/Z\/18\/Z"],"award-info":[{"award-number":["210462\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223743\/Z\/21\/Z"],"award-info":[{"award-number":["223743\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00034\/8"],"award-info":[{"award-number":["MC_UU_00034\/8"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00034\/7"],"award-info":[{"award-number":["MC_UU_00034\/7"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12014\/8"],"award-info":[{"award-number":["MC_UU_12014\/8"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00034\/4"],"award-info":[{"award-number":["MC_UU_00034\/4"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00034\/5\/RCUK"],"award-info":[{"award-number":["MC_UU_00034\/5\/RCUK"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020894","name":"School of Veterinary Medicine, University of Glasgow","doi-asserted-by":"publisher","award":["Andrew Clarke Endowement"],"award-info":[{"award-number":["Andrew Clarke Endowement"]}],"id":[{"id":"10.13039\/501100020894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Bhanja virus (BHAV) is a tick-borne bandavirus (Family\n                    <jats:italic>Phenuiviridae<\/jats:italic>\n                    ) with a broad geographic distribution and documented neuroinvasive capacity, yet its molecular biology remains poorly understood. Within the genus\n                    <jats:italic>Bandavirus<\/jats:italic>\n                    , the non-structural protein NSs functions as the primary antagonist of innate immune responses, although mechanistic details for BHAV remain unknown. We established a reverse genetics platform for BHAV by combining virion RNA sequencing with terminal untranslated region mapping, enabling generation of recombinant viruses and systematic investigation of viral determinants. Using this system, we characterized recombinant BHAV replication in mammalian and arthropod cell lines and demonstrated that interferon competence is a critical determinant of viral replication in mammalian cells. Notably, we observed substantial amino acid divergence within the NSs protein across geographically distinct BHAV isolates, despite higher conservation of other viral proteins. To investigate the functional significance of this variation, we generated recombinant viruses expressing heterologous NSs proteins from African and European isolates. Viruses expressing NSs from ibAr2709 or R1819 isolates exhibited enhanced capacity to suppress interferon-beta induction compared to the prototype IG690 strain, correlating with increased viral protein accumulation in interferon-competent cells. Mechanistic studies revealed that BHAV NSs proteins inhibit interferon induction upstream of IRF3, with ibAr2709 and R1819 NSs showing selective inhibition of TBK1 phosphorylation. However, unlike highly pathogenic bandaviruses such as severe fever with thrombocytopenia syndrome virus (SFTSV), BHAV NSs proteins exhibit comparatively weak antagonism of downstream interferon signalling.\n                    <jats:italic>In vivo<\/jats:italic>\n                    studies using interferon alpha\/beta receptor-deficient mice demonstrated that NSs sequence variation influences viral replication in splenic tissue without substantially altering disease phenotype. Together, these findings establish BHAV reverse genetics tools for future investigation and reveal how naturally-occurring NSs divergence modulates innate immune antagonism and viral fitness while maintaining an overall attenuated disease phenotype.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014645","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:49:12Z","timestamp":1790272152000},"page":"e1014645","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional divergence of the Bhanja virus NSs protein modulates interferon antagonism and viral fitness across divergent lineages"],"prefix":"10.1371","volume":"22","author":[{"given":"Andrew T.","family":"Clarke","sequence":"first","affiliation":[{"name":"Medical Research Council\u2013University of Glasgow Centre for Virus Research","place":["Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Davies","sequence":"additional","affiliation":[{"name":"Medical Research Council\u2013University of Glasgow Centre for Virus Research","place":["Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazigh","family":"Fares","sequence":"additional","affiliation":[{"name":"Medical Research Council\u2013University of Glasgow Centre for Virus Research","place":["Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka M.","family":"Szemiel","sequence":"additional","affiliation":[{"name":"Medical Research Council\u2013University of Glasgow Centre for Virus Research","place":["Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo","family":"Correa Mendonca","sequence":"additional","affiliation":[{"name":"CVR Translational Hub, MRC-University of Glasgow Centre for Virus Research","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kerr","sequence":"additional","affiliation":[{"name":"CVR Translational Hub, MRC-University of Glasgow Centre for Virus Research","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Herder","sequence":"additional","affiliation":[{"name":"CVR Translational Hub, MRC-University of Glasgow Centre for Virus Research","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Bell-Sakyi","sequence":"additional","affiliation":[{"name":"University of Liverpool","place":["Liverpool, United Kingdom"],"department":["Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Willett","sequence":"additional","affiliation":[{"name":"Medical Research Council\u2013University of Glasgow Centre for Virus Research","place":["Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-2047","authenticated-orcid":true,"given":"Arvind H.","family":"Patel","sequence":"additional","affiliation":[{"name":"CVR Translational Hub, MRC-University of Glasgow Centre for Virus Research","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Kohl","sequence":"additional","affiliation":[{"name":"Medical Research Council\u2013University of Glasgow Centre for Virus Research","place":["Scotland, United Kingdom"]},{"name":"Liverpool School of Tropical Medicine, Centre for Neglected Tropical Diseases","place":["Liverpool, United Kingdom"],"department":["Departments of Tropical Disease Biology and Vector Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4707-726X","authenticated-orcid":true,"given":"Benjamin","family":"Brennan","sequence":"additional","affiliation":[{"name":"Medical Research Council\u2013University of Glasgow Centre for Virus Research","place":["Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ppat.1014645.ref001","first-page":"793","article-title":"Bhanja virus: A new arbovirus from ticks Haemaphysalis intermedia Warburton and Nuttall, 1909, in Orissa, India","volume":"57","author":"KV Shah","year":"1969","journal-title":"Indian J Med Res"},{"issue":"1","key":"ppat.1014645.ref002","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4269\/ajtmh.1970.19.103","article-title":"Isolation of Bhanja virus from Haemaphysalis ticks in Italy","volume":"19","author":"P Verani","year":"1970","journal-title":"Am J Trop Med Hyg"},{"key":"ppat.1014645.ref003","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.4269\/ajtmh.1977.26.1003","article-title":"Isolation of Bhanja virus from ticks in Yugoslavia","volume":"26","author":"J Vesenjak-Hirjan","year":"1977","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"ppat.1014645.ref004","first-page":"67","article-title":"Isolation of Bhanja virus from ticks of the genus Haemaphysalis in southeast Bulgaria and presence of antibodies in pastured sheep","volume":"25","author":"P Pavlov","year":"1978","journal-title":"Folia Parasitol"},{"key":"ppat.1014645.ref005","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/BF01311000","article-title":"Isolation of \u201cexotic\u201d Bhanja virus (Bunyaviridae) from ticks in the temperate zone","volume":"101","author":"Z Hub\u00e1lek","year":"1988","journal-title":"Arch Virol"},{"issue":"2","key":"ppat.1014645.ref006","first-page":"139","article-title":"Isolation of Bhanja virus in Romania","volume":"49","author":"A Ungureanu","year":"1990","journal-title":"Arch Roum Pathol Exp Microbiol"},{"issue":"5","key":"ppat.1014645.ref007","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/jmedent\/9.5.443","article-title":"Ixodid ticks from domestic livestock in Ibadan, Nigeria as carriers of viral agents","volume":"9","author":"RW Williams","year":"1972","journal-title":"J Med Entomol"},{"key":"ppat.1014645.ref008","first-page":"28","article-title":"Surgey of tick-borne arboviruses in the Central African Republic (1973-1974). 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An account of the Rockefeller Foundation virus program, 1951-1970","author":"M Theiler","year":"1973"},{"key":"ppat.1014645.ref017","first-page":"284","article-title":"Experimental pathogenicity of Bhanja virus","volume":"266","author":"Z Hub\u00e1lek","year":"1987","journal-title":"Zentralbl Bakteriol Mikrobiol Hyg A"},{"key":"ppat.1014645.ref018","first-page":"184","article-title":"Experimental pathogenicity of Bhanja virus for lambs at different infection routes.","volume-title":"Ecology of viruses","author":"IV Semashko","year":"1976"},{"issue":"3","key":"ppat.1014645.ref019","first-page":"257","article-title":"Ecological and nosological study of tick-borne arboviruses in Senegal. II. Experimental study of the pathogenicity of the Bhanja virus in small domestic ruminants","volume":"34","author":"JL Camicas","year":"1981","journal-title":"Rev Elev Med Vet Pays Trop"},{"issue":"1","key":"ppat.1014645.ref020","first-page":"79","article-title":"Experimental infection of sheep with Bhanja virus","volume":"31","author":"V M\u00e1dr","year":"1984","journal-title":"Folia Parasitol"},{"key":"ppat.1014645.ref021","first-page":"297","article-title":"First natural clinical human Bhanja virus infection","volume":"9","author":"J Vesenjak-Hirjan","year":"1980","journal-title":"Zentralbl Bakteriol"},{"key":"ppat.1014645.ref022","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.4269\/ajtmh.1975.24.1040","article-title":"Human infection with Bhanja virus","volume":"24","author":"CH Calisher","year":"1975","journal-title":"Am J Trop Med Hyg"},{"key":"ppat.1014645.ref023","first-page":"297","article-title":"Laboratory infections with Bhanja virus","author":"V 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