{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T06:32:52Z","timestamp":1766212372969,"version":"3.48.0"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2018\/10990-1"],"award-info":[{"award-number":["2018\/10990-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2021\/05519-0"],"award-info":[{"award-number":["2021\/05519-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Brazilian Ministry of Science and Technology"},{"name":"Pew Charitable Trust and Chan Zuckerberg initiative Foundation"},{"name":"FAPESP scholarships","award":["2018\/02594-9"],"award-info":[{"award-number":["2018\/02594-9"]}]},{"name":"FAPESP scholarships","award":["2019\/06459-1"],"award-info":[{"award-number":["2019\/06459-1"]}]},{"name":"FAPESP scholarships","award":["2022\/02278-5"],"award-info":[{"award-number":["2022\/02278-5"]}]},{"name":"FAPESP scholarships","award":["2022\/01379-2"],"award-info":[{"award-number":["2022\/01379-2"]}]},{"name":"CNPq scholarship","award":["141253\/2019-3"],"award-info":[{"award-number":["141253\/2019-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Usutu virus (USUV) is an emerging arbovirus recently associated with outbreaks in Western Europe. Although USUV is typically associated with asymptomatic or nonspecific febrile disease, the occurrence of severe neuroinvasive forms of disease has raised concern. There is currently no antiviral treatment available for USUV infection; therefore, we sought to investigate the protective effects of the nucleoside analogue 7DMA against USUV. Adding to 7DMA\u2019s activity against USUV in vitro reported by us and others, we found that 7DMA inhibits USUV replication at multiple stages in mammalian cell lines Vero CCL81 and SH-SY5Y. In vivo testing of 7DMA using the susceptible IFNAR-\/- mouse model indicated that 7DMA treatment significantly reduced USUV viremia and viral load in tissues and prolonged mice survival. The characterization of the protective effects of 7DMA indicated that treatment also altered immunological aspects of disease development, further increasing the expression of mediators such as CXCL10, IL-15, and IFN-\u03b3, and increasing neutrophil recruitment to target organs. We did not observe significant tissue damage or pathology in USUV-infected mouse brains, suggesting that systemic infection and disease are the major components leading to mortality in this model. We conclude that 7DMA exerts protective effects against USUV infection in the IFNAR-\/- model.<\/jats:p>","DOI":"10.3390\/v17121639","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T11:08:28Z","timestamp":1766056108000},"page":"1639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antiviral and Immunomodulatory Effects of 7-Deaza-2-methyladenosine (7DMA) in a Susceptible Mouse Model of Usutu Virus Infection"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5678-4006","authenticated-orcid":false,"given":"Rebeca P. F.","family":"Rocha","sequence":"first","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1192-7210","authenticated-orcid":false,"given":"Marina A.","family":"Fontoura","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-8821","authenticated-orcid":false,"given":"Fabr\u00edcio","family":"Naciuk","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1267-4569","authenticated-orcid":false,"given":"Alice","family":"Nagai","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-3103","authenticated-orcid":false,"given":"Amanda Bellini","family":"Silva","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"},{"name":"Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Borin","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"},{"name":"Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaqueline S.","family":"Felipe","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"},{"name":"Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4236-848X","authenticated-orcid":false,"given":"Marjorie","family":"Bruder","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lais D.","family":"Coimbra","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6949-0947","authenticated-orcid":false,"given":"Rafael Elias","family":"Marques","sequence":"additional","affiliation":[{"name":"Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP 13083-100, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.molmed.2025.05.010","article-title":"Priorities for Modelling Arbovirus Transmission under Climate Change","volume":"31","author":"Dorigatti","year":"2025","journal-title":"Trends Mol. 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