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Infection results in profound immunosuppression, neurological dysfunction, and the development of malignant T\u2010cell lymphomas. Continued viral evolution has produced increasingly virulent strains capable of partially or fully evading current vaccines, leaving few options for controlling emerging variants. This highlights the importance of identifying new antiviral targets, particularly those involved in the nuclear trafficking events essential for GaAHV2 replication. The UL36 large tegument protein of alphaherpesviruses contains N\u2010terminal nuclear localization signals (NLSs) thought to guide capsid transport to the nuclear pore complex. However, the specific mechanism by which GaAHV2 UL36 engages the host nuclear import machinery remains unclear. In this work, we defined the NLS within the N\u2010terminal region of GaAHV2 UL36 and characterized its interaction with importin proteins. Through high\u2010resolution crystallography and quantitative binding assays, we pinpointed the residues and structural motifs within UL36 that mediate recognition by importin\u2010\u03b1 (IMP\u03b1) and compared their affinities across different IMP\u03b1 isoforms. Our structural and biochemical data show that the predicted N\u2010terminal NLS of GaAHV2 UL36 is essential for IMP\u03b1 binding. These findings provide a detailed molecular framework for host\u2013virus interactions during GaAHV2 nuclear entry and offer potential avenues for the development of targeted antiviral strategies.<\/jats:p>","DOI":"10.1155\/av\/8716375","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:30:29Z","timestamp":1782109829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural Insights Into the Nuclear Import of Marek\u2019s Disease Virus Large Tegument Protein"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3620-1181","authenticated-orcid":false,"given":"Babu Kanti","family":"Nath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate H. 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