{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:53:52Z","timestamp":1785430432140,"version":"3.56.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AI1321"],"award-info":[{"award-number":["T32 AI1321"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Thogotoviruses are arthropod-borne viruses belonging to the genus\n                      <jats:italic toggle=\"yes\">Thogotovirus<\/jats:italic>\n                      within the family\n                      <jats:italic toggle=\"yes\">Orthomyxoviridae<\/jats:italic>\n                      . Like other orthomyxoviruses, such as the influenza A viruses (IAV), thogotoviruses replicate in the nucleus. As a result, progeny viral ribonucleoprotein complexes (vRNPs) must be exported to the cytoplasm prior to virion assembly and budding at the plasma membrane. In IAV, this export depends on binding of the viral nuclear export protein (NEP) to the cellular exportin chromosomal maintenance 1 (CRM1). In contrast, the mechanism of vRNP nuclear export, including identification of a protein with NEP functionality, has not been characterized for any thogotoviruses. Here, we characterized vRNP nuclear export in Dhori virus (DHOV), a prototypic member of the\n                      <jats:italic toggle=\"yes\">Thogotovirus<\/jats:italic>\n                      genus. DHOV replication and nuclear export of the viral nucleoprotein were inhibited by the canonical CRM1 inhibitor leptomycin B (LMB), suggesting that DHOV vRNP export also utilizes CRM1. Interestingly, LMB treatment led to nuclear retention of the DHOV matrix (M) protein in both infected and transfected cells. Using a mammalian two-hybrid system, we found that DHOV M interacts with CRM1 through a nuclear export sequence (NES) located between amino acids 111 and 128. Mutation of hydrophobic residues within this NES reduced M-CRM1 interaction, abolished the NES phenotype when fused to a fluorescent protein, and impaired rescue of recombinant DHOV by reverse genetics. Together, our results reveal that DHOV vRNP nuclear export is CRM1-dependent and mediated by the M protein rather than a dedicated NEP-like protein, providing the first mechanistic insight into vRNP egress in the genus\n                      <jats:italic toggle=\"yes\">Thogotovirus<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Dhori virus (DHOV) is a pathogenic tick-borne virus in the genus\n                      <jats:italic toggle=\"yes\">Thogotovirus<\/jats:italic>\n                      , in the family Orthomyxoviridae. Despite evidence of DHOV exposure in various mammals, including humans, its basic biology is not well understood. We investigated how DHOV\u2019s progeny genome and protein complexes\u2014viral ribonucleoprotein complexes (vRNPs)\u2014are transported out of the nucleus. Our findings show that DHOV, like the influenza viruses, uses the cellular protein chromosomal maintenance protein 1 (CRM1) for vRNP export. We found that chemically inhibiting CRM1 completely blocked DHOV vRNP export, preventing the production of progeny viruses from infected cells. Screening of all known DHOV proteins revealed that the matrix protein, which forms the virus\u2019 scaffold, interacted with CRM1, suggesting it may link CRM1 to the vRNPs. These results advance our understanding of DHOV replication and suggest that chemically inhibiting vRNP export could be a way to treat thogotovirus infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01494-25","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T14:23:56Z","timestamp":1764685436000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Involvement of a tick-borne orthomyxovirus matrix protein in vRNP nuclear export"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1706-1833","authenticated-orcid":true,"given":"Vaille A.","family":"Swenson","sequence":"first","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences","place":["Rochester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Hemsath","sequence":"additional","affiliation":[{"name":"Kansas City University College of Osteopathic Medicine, Farber McIntire Campus","place":["Joplin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Yousaf","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qp3tb03","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Medicine, Mayo Clinic","place":["Rochester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Weisend","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qp3tb03","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Medicine, Mayo Clinic","place":["Rochester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Barry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qp3tb03","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Mayo Clinic","place":["Rochester, USA"]},{"id":[{"id":"https:\/\/ror.org\/02qp3tb03","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Mayo Clinic","place":["Rochester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-9735","authenticated-orcid":false,"given":"Hideki","family":"Ebihara","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001ggbx22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Virology 1, National Institute of Infectious Diseases","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9768-5696","authenticated-orcid":true,"given":"Satoko","family":"Yamaoka","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02qp3tb03","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Mayo Clinic","place":["Rochester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001887"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01556-21"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1975.11686983"},{"key":"e_1_3_3_5_2","first-page":"724","article-title":"Dhori virus--a causative agent of human disease. 5 cases of laboratory infection","volume":"32","author":"Butenko AM","year":"1987","unstructured":"Butenko AM, Leshchinskaia EV, Semashko IV, Donets MA, Mart\u2019ianova LI. 1987. 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