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Recent outbreaks of mpox underscore the need for a better understanding of poxvirus biology\n                    <jats:sup>1,2<\/jats:sup>\n                    . Poxvirus assembly is a conserved process that involves the formation of a biconcave core inside the membrane of the maturing virus\n                    <jats:sup>3,4<\/jats:sup>\n                    . Here we use cryo-electron tomography combined with subtomogram averaging and structure prediction to determine the structure and composition of the portal complex\u2014a pore that spans the core wall\u2014in vaccinia virus, the prototypical poxvirus. The hexameric complex consists of the E8, E6 and L3 proteins, which are conserved across poxviruses and essential for mRNA release during the establishment of infection\n                    <jats:sup>5\u20137<\/jats:sup>\n                    . E6, which is also required for virus assembly\n                    <jats:sup>8\u201310<\/jats:sup>\n                    , forms the central chamber of the portal and interacts with the surrounding core wall. A hexamer of E8 attaches to the exterior side of E6. L3, a target of TRIM5\u03b1-mediated restriction\n                    <jats:sup>11<\/jats:sup>\n                    , binds as a hexamer of dimers to the interior side. Furthermore, the viral helicase D5, which is required for genome release from cores\n                    <jats:sup>12<\/jats:sup>\n                    , associates with cytoplasmic cores during infection by docking onto the exterior E8 rim of the portal complex. We propose that the portal complex represents an attractive target for the development of anti-poxvirus therapeutics.\n                  <\/jats:p>","DOI":"10.1038\/s41586-026-10856-2","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:02:05Z","timestamp":1785337325000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In situ structure of the poxvirus portal complex"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5716-0270","authenticated-orcid":false,"given":"Thomas","family":"Calcraft","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-7076","authenticated-orcid":false,"given":"Miguel","family":"Hernandez-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-2722","authenticated-orcid":false,"given":"Michael","family":"Way","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0387-2862","authenticated-orcid":false,"given":"Peter B.","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"10856_CR1","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1038\/s41564-024-01690-1","volume":"9","author":"B Moss","year":"2024","unstructured":"Moss, B. Understanding the biology of monkeypox virus to prevent future outbreaks. Nat. Microbiol. 9, 1408\u20131416 (2024).","journal-title":"Nat. Microbiol."},{"key":"10856_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/v13010043","volume":"13","author":"NI Oliveira Silva","year":"2020","unstructured":"Oliveira Silva, N. I., Silva de Oliveira, J., Kroon, E. G., de Souza Trindade, G. & Drumond, B. P. Here, there, and everywhere: the wide host range and geographic distribution of zoonotic orthopoxviruses. Viruses 13, 43 (2020).","journal-title":"Viruses"},{"key":"10856_CR3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0065-3527(06)66002-8","volume":"66","author":"RC Condit","year":"2006","unstructured":"Condit, R. C., Moussatche, N. & Traktman, P. In a nutshell: structure and assembly of the vaccinia virion. Adv. Virus Res. 66, 31\u2013124 (2006).","journal-title":"Adv. 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