{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T13:33:33Z","timestamp":1777037613468,"version":"3.51.4"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":258,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Italian Ministry for Universities and Research","doi-asserted-by":"crossref","award":["C53D23003110006"],"award-info":[{"award-number":["C53D23003110006"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Training Hub promoting Regional Industry and Innovation in Virology and Epidemiology","award":["DE200100367"],"award-info":[{"award-number":["DE200100367"]}]},{"name":"EU within the NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Anelloviridae members are ubiquitous viruses with a small, negative sense, single-stranded DNA genome which is replicated by host cell DNA polymerases. Anelloviruses are postulated to interact with the host cell nuclear transport machinery, however, the lack of reliable cell culture models strongly limits our knowledge regarding Anelloviridae-host interactions. In particular, capsid nuclear import is a largely uncharacterized process. We addressed this by investigating the relationship between host cell nuclear transport receptors (NTRs) and ORF1, the putative capsid protein from torque teno douroucouli virus (TTDoV). We identified the subcellular targeting signals and NTRs responsible for its nucleolar and nuclear localization, and characterized their relative contribution to ORF1 subcellular localization. In the absence of other viral proteins, ORF1 accumulated in the nucleoli. Bioinformatics analysis revealed a putative classical nuclear localization signal (cNLS) within the highly conserved N-terminal arginine rich motif (ARM) (\u2018NLSn\u2019, 27-RRWRRRPRRRRRPYRRRPYRRYGRRRKVRRR-57), and an additional C-terminal cNLS (\u2018NLSc\u2019, 632-LPPPEKRARWGF-643), which has been specifically acquired by Anelloviridae capsids with larger projection domains. Such NLSs play distinct roles in ORF1 subcellular localization by interacting with specific NTRs. NLSn, a non-classical NLS, features broad importin (IMP) binding affinity yet plays a minor role in nuclear import, being responsible for nucleolar targeting likely through interaction with nucleolar components. NLSc, a bona fide cNLS, specifically interacts with IMP\u03b1 and is the main driver of active nuclear transport in an IMP\u03b1\/\u03b21-dependent fashion. These findings suggest an evolutionary correlation between the acquisition of progressively larger projection domains and the presence of additional cNLSs in Anelloviridae capsids, aimed at maximizing IMP\u03b1\/\u03b21-mediated nuclear import.<\/jats:p>","DOI":"10.1093\/ve\/veaf069","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T21:40:42Z","timestamp":1758318042000},"source":"Crossref","is-referenced-by-count":7,"title":["Nuclear trafficking of <i>Anelloviridae<\/i> capsid protein ORF1 reflects modular evolution of subcellular targeting signals"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3666-0150","authenticated-orcid":false,"given":"Gayle F","family":"Petersen","sequence":"first","affiliation":[{"name":"Gulbali Institute, Charles Sturt University , 250 Boorooma Street, Wagga Wagga, NSW 2678 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Pavan","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova , Via Gabelli 63, Padova (PD) 35121 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryl","family":"Ariawan","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 75 Talavera Rd, Macquarie University , Sydney, NSW 2109 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8781-256X","authenticated-orcid":false,"given":"Ole","family":"Tietz","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 75 Talavera Rd, Macquarie University , Sydney, NSW 2109 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sepehr","family":"Nematollahzadeh","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova , Via Gabelli 63, Padova (PD) 35121 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subir","family":"Sarker","sequence":"additional","affiliation":[{"name":"Biomedical Sciences & Molecular Biology, College of Medicine and Dentistry, James Cook University , 1 James Cook drive, Townsville, QLD 4811 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jade K","family":"Forwood","sequence":"additional","affiliation":[{"name":"Gulbali Institute, Charles Sturt University , 250 Boorooma Street, Wagga Wagga, NSW 2678 ,","place":["Australia"]},{"name":"School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University , 250 Boorooma Street, Wagga Wagga, NSW 2678 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