{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:06:41Z","timestamp":1785434801795,"version":"3.56.0"},"reference-count":158,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82102431"],"award-info":[{"award-number":["82102431"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82102431"],"award-info":[{"award-number":["82102431"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province, China","doi-asserted-by":"crossref","award":["26JRRA817"],"award-info":[{"award-number":["26JRRA817"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Longyuan Young Talents Program of Gansu Province, China"},{"name":"Key Incubation Project Funds of The Second Hospital & Clinical Medical School, Lanzhou University","award":["2025-21-zdfy-004"],"award-info":[{"award-number":["2025-21-zdfy-004"]}]},{"award":["2025-21-zdfy-004"],"award-info":[{"award-number":["2025-21-zdfy-004"]}],"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Talent Introduction Plan of The Second Hospital & Clinical Medical School, Lanzhou University","award":["yjrckyqdj-2021-03"],"award-info":[{"award-number":["yjrckyqdj-2021-03"]}]},{"award":["yjrckyqdj-2021-03"],"award-info":[{"award-number":["yjrckyqdj-2021-03"]}],"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>O\u2019nyong-nyong virus (ONNV) is a mosquito-borne alphavirus responsible for large-scale epidemics in sub-Saharan Africa. As the closest evolutionary relative of Chikungunya virus (CHIKV), ONNV shares substantial genetic similarity and overlapping clinical manifestations with CHIKV. Mechanistic understanding of ONNV infection has therefore largely been extrapolated from CHIKV rather than directly established. However, ONNV exhibits distinct biological features, including predominant transmission by Anopheles mosquitoes and a clinical presentation characterized by prominent lymphadenopathy with limited acute joint edema. These distinctions underscore the need for an integrated synthesis of experimentally validated determinants of ONNV infection. In this review, we summarize current evidence on molecular and immunological factors regulating ONNV infection in mammalian hosts and mosquito vectors. We first discuss species-specific viral clearance, host dependency factors, intrinsic antiviral restriction mechanisms, protective innate immunity, inflammatory pathology, and mechanism-informed therapeutic strategies in mammalian hosts. We then examine stage-specific immune regulation in Anopheles mosquitoes, emphasizing mechanisms that constrain viral replication while permitting persistent infection and transmission. Finally, we discuss nsP3-dependent vector specificity and the potential contribution of alternative mosquito species to ONNV ecology. Together, this review provides an integrated framework for understanding how host factors, immune responses, and vector-specific adaptations shape ONNV infection, pathogenesis, and transmission.<\/jats:p>","DOI":"10.3390\/biom16060904","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:25:34Z","timestamp":1781778334000},"page":"904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Determinants of O\u2019Nyong-Nyong Virus Infection in Mammalian Hosts and Anopheles Mosquitoes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1326-264X","authenticated-orcid":false,"given":"Zhiyuan","family":"Liu","sequence":"first","affiliation":[{"name":"Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China"},{"name":"School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwen","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangyu","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0100-1489","authenticated-orcid":false,"given":"Jianli","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5414-2141","authenticated-orcid":false,"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China"},{"name":"School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1099\/jgv.0.001072","article-title":"ICTV Virus Taxonomy Profile: Togaviridae","volume":"99","author":"Chen","year":"2018","journal-title":"J. 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