{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T07:57:50Z","timestamp":1791705470542,"version":"4.3.4"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"23","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (VACV;\n            <jats:named-content content-type=\"genus-species\">Poxviridae<\/jats:named-content>\n            ). VACV strain IOC (VACV-IOC) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in Brazil during the smallpox eradication program. However, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. In this work, we present a comprehensive characterization of two clones of VACV-IOC. Both clones had low virulence in infected mice and induced a protective immune response against a lethal infection comparable to the response of the licensed vaccine ACAM2000 and the parental strain VACV-IOC. Full-genome sequencing revealed the presence of several fragmented virulence genes that probably are nonfunctional, e.g., F1L, B13R, C10L, K3L, and C3L. Most notably, phylogenetic inference supported by the structural analysis of the genome ends provides evidence of a novel, independent cluster in VACV phylogeny formed by VACV-IOC, the Brazilian field strains Cantagalo (CTGV) and Serro 2 viruses, and horsepox virus, a VACV-like virus supposedly related to an ancestor of the VACV lineage. Our data strongly support the hypothesis that CTGV-like viruses represent feral VACV that evolved in parallel with VACV-IOC after splitting from a most recent common ancestor, probably an ancient smallpox vaccine strain related to horsepox virus. Our data, together with an interesting historical investigation, revisit the origins of VACV and propose new evolutionary relationships between ancient and extant VACV strains, mainly horsepox virus, VACV-IOC\/CTGV-like viruses, and Dryvax strain.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            First-generation vaccines used to eradicate smallpox had rates of adverse effects that are not acceptable by current health care standards. Moreover, these vaccines are genetically heterogeneous and consist of a pool of quasispecies of VACV. Therefore, the search for new-generation smallpox vaccines that combine low pathogenicity, immune protection, and genetic homogeneity is extremely important. In addition, the phylogenetic relationships and origins of VACV strains are quite nebulous. We show the characterization of two clones of VACV-IOC, a unique smallpox vaccine strain that contributed to smallpox eradication in Brazil. The immunogenicity and reduced virulence make the IOC clones good options for alternative second-generation smallpox vaccines. More importantly, this study reveals the phylogenetic relationship between VACV-IOC, feral VACV established in nature, and the ancestor-like horsepox virus. Our data expand the discussion on the origins and evolutionary connections of VACV lineages.\n          <\/jats:p>","DOI":"10.1128\/jvi.01833-15","type":"journal-article","created":{"date-parts":[[2015,9,17]],"date-time":"2015-09-17T03:38:17Z","timestamp":1442461097000},"page":"11909-11925","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus"],"prefix":"10.1128","volume":"89","author":[{"given":"Maria Luiza G.","family":"Medaglia","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de V\u00edrus, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nissin","family":"Moussatch\u00e9","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Nitsche","sequence":"additional","affiliation":[{"name":"Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pjotr Wojtek","family":"Dabrowski","sequence":"additional","affiliation":[{"name":"Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger K.","family":"Damon","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina G. O.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Departamento de Virologia, Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana B.","family":"Arruda","sequence":"additional","affiliation":[{"name":"Departamento de Virologia, Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa R.","family":"Damaso","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de V\u00edrus, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Smallpox and its eradication","author":"Fenner F","year":"1988","unstructured":"Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID. 1988. 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