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However, resting T cells are highly refractory to cell-free virus infection in vitro\n                    <jats:sup>5\u20137<\/jats:sup>\n                    and require mitogenic activation to become permissive. This paradox raises the fundamental question of what makes a T cell permissive for HIV-1. Here we address this and show that HIV-1 capsid nuclear import at the nuclear pore complex (NPC) is a bottleneck to resting T cell infection, but that HIV-1 overcomes this by triggering receptor-mediated signalling during cell\u2013cell spread to drive nuclear import and licence infection. Coupling viral and cellular assays with super-resolution imaging, we show that contact between HIV-1 infected and uninfected T cells triggers CD4\u2013LCK signalling that activates CDK1, independent of cell-cycle entry, phosphorylating nucleoporins and priming the NPC to promote HIV-1 nuclear import. Critically, cell\u2013cell contact also accelerates nuclear import in activated T cells, providing a paradigm for why cell\u2013cell spread dominates infection. By contrast, HIV-1 virions do not trigger this response, explaining why resting T cells cannot be efficiently infected by cell-free virus. We propose that HIV-1 has evolved to selectively activate CD4 signalling during cell\u2013cell spread to regulate infection at the step of the NPC, offering an explanation for how resting T cells can be infected in vivo.\n                  <\/jats:p>","DOI":"10.1038\/s41586-026-10453-3","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:03:30Z","timestamp":1778079810000},"page":"1044-1054","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["HIV-1 signalling remodels nuclear pores to licence infection"],"prefix":"10.1038","volume":"654","author":[{"given":"Dejan","family":"Mesner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew V. X.","family":"Whelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maitreyi","family":"Shivkumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Kathrin","family":"Reuschl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo Zenezini","family":"Chiozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-8428","authenticated-orcid":false,"given":"Konstantinos","family":"Thalassinos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-1409","authenticated-orcid":false,"given":"Robertus A. 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