{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:51:39Z","timestamp":1773658299067,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T00:00:00Z","timestamp":1443052800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T00:00:00Z","timestamp":1443052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Horizontal gene transfer from retroviruses to mammals is well documented and extensive, but is rare between unrelated viruses with distinct genome types. Three herpesviruses encode a gene with similarity to a retroviral superantigen gene (<jats:italic>sag<\/jats:italic>) of the unrelated mouse mammary tumour virus (MMTV). We uncover ancient retroviral <jats:italic>sags<\/jats:italic> in over 20 mammals to reconstruct their shared history with herpesviral <jats:italic>sags<\/jats:italic>, revealing that the acquisition is a convergent evolutionary event. A retrovirus circulating in South American primates over 10 million years ago was the source of <jats:italic>sag<\/jats:italic> in two monkey herpesviruses, and a different retrovirus was the source of <jats:italic>sag<\/jats:italic> in a Peruvian rodent herpesvirus. We further show through a timescaled phylogenetic analysis that a cross-species transmission of monkey herpesviruses occurred after the acquisition of <jats:italic>sag<\/jats:italic>. These results reveal that a diverse range of ancient <jats:italic>sag-<\/jats:italic>containing retroviruses independently donated <jats:italic>sag<\/jats:italic> twice from two separate lineages that are distinct from MMTV.<\/jats:p>","DOI":"10.1038\/ncomms9299","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T09:08:02Z","timestamp":1443085682000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Convergent capture of retroviral superantigens by mammalian herpesviruses"],"prefix":"10.1038","volume":"6","author":[{"given":"Amr","family":"Aswad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aris","family":"Katzourakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,9,24]]},"reference":[{"key":"BFncomms9299_CR1","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.4049\/jimmunol.1203130","volume":"192","author":"J-S Fortin","year":"2014","unstructured":"Fortin, J.-S. et al. MMTV superantigens coerce an unconventional topology between the TCR and MHC class II. J. Immunol. 192, 1896\u20131906 (2014).","journal-title":"J. Immunol."},{"key":"BFncomms9299_CR2","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1111\/j.1600-065X.2008.00681.x","volume":"225","author":"JD Fraser","year":"2008","unstructured":"Fraser, J. D. & Proft, T. The bacterial superantigen and superantigen-like proteins. Immunol. Rev. 225, 226\u2013243 (2008).","journal-title":"Immunol. Rev."},{"key":"BFncomms9299_CR3","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/S1473-3099(02)00222-0","volume":"2","author":"M Llewelyn","year":"2002","unstructured":"Llewelyn, M. & Cohen, J. Superantigens: microbial agents that corrupt immunity. Lancet Infect. Dis. 2, 156\u2013162 (2002).","journal-title":"Lancet Infect. Dis."},{"key":"BFncomms9299_CR4","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1146\/annurev.iy.13.040195.002331","volume":"13","author":"H Acha-Orbea","year":"1995","unstructured":"Acha-Orbea, H. & MacDonald, H. R. Superantigens of mouse mammary tumor virus. Annu. Rev. Immunol. 13, 459\u2013486 (1995).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms9299_CR5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1128\/jvi.46.1.42-49.1983","volume":"46","author":"DA Wheeler","year":"1983","unstructured":"Wheeler, D. A., Butel, J. S., Medina, D., Cardiff, R. D. & Hager, G. L. Transcription of mouse mammary tumor virus: identification of a candidate mRNA for the long terminal repeat gene product. J. Virol. 46, 42\u201349 (1983).","journal-title":"J. Virol."},{"key":"BFncomms9299_CR6","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/jvi.46.2.362-370.1983","volume":"46","author":"AJ van Ooyen","year":"1983","unstructured":"van Ooyen, A. J., Michalides, R. J. & Nusse, R. Structural analysis of a 1.7-kilobase mouse mammary tumor virus-specific RNA. J. Virol. 46, 362\u2013370 (1983).","journal-title":"J. Virol."},{"key":"BFncomms9299_CR7","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4049\/jimmunol.152.3.1032","volume":"152","author":"CD Jarvis","year":"1994","unstructured":"Jarvis, C. D., Germain, R. N., Hager, G. L., Damschroder, M. & Matis, L. A. Tissue-specific expression of messenger RNAs encoding endogenous viral superantigens. J. Immunol. 152, 1032\u20131038 (1994).","journal-title":"J. Immunol."},{"key":"BFncomms9299_CR8","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1128\/jvi.71.2.1237-1245.1997","volume":"71","author":"J Arroyo","year":"1997","unstructured":"Arroyo, J., Winchester, E., McLellan, B. & Huber, B. Shared promoter elements between a viral superantigen and the major histocompatibility complex class II-associated invariant chain. J. Virol. 71, 1237\u20131245 (1997).","journal-title":"J. Virol."},{"key":"BFncomms9299_CR9","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/364154a0","volume":"364","author":"WH G\u00fcnzburg","year":"1993","unstructured":"G\u00fcnzburg, W. H. et al. Endogenous superantigen expression controlled by a novel promoter in the MMTV long terminal repeat. Nature 364, 154\u2013158 (1993).","journal-title":"Nature"},{"key":"BFncomms9299_CR10","doi-asserted-by":"crossref","unstructured":"McGeoch, D. J., Davison, A. J., Dolan, A., Gatherer, D. & Sevilla-Reyes, E. E. in Origin and Evolution of Viruses eds Domingo E., Holland J. J. 447\u2013475Academic Press (2008).","DOI":"10.1016\/B978-0-12-374153-0.00020-5"},{"key":"BFncomms9299_CR11","unstructured":"Fields, B. N., Knipe, D. M. & Howley, P. M. Fields Virology. Virology Lippincott Williams and Wilkins (2007)."},{"key":"BFncomms9299_CR12","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1128\/JVI.74.2.1033-1037.2000","volume":"74","author":"J-C Albrecht","year":"2000","unstructured":"Albrecht, J.-C. Primary structure of the herpesvirus ateles genome. J. Virol. 74, 1033\u20131037 (2000).","journal-title":"J. Virol."},{"key":"BFncomms9299_CR13","doi-asserted-by":"crossref","first-page":"5047","DOI":"10.1128\/jvi.66.8.5047-5058.1992","volume":"66","author":"JC Albrecht","year":"1992","unstructured":"Albrecht, J. C. et al. Primary structure of the herpesvirus saimiri genome. J. Virol. 66, 5047\u20135058 (1992).","journal-title":"J. Virol."},{"key":"BFncomms9299_CR14","doi-asserted-by":"publisher","first-page":"2642","DOI":"10.1128\/JVI.01661-10","volume":"85","author":"J Loh","year":"2011","unstructured":"Loh, J. et al. Identification and sequencing of a novel rodent gammaherpesvirus that establishes acute and latent infection in laboratory mice. J. Virol. 85, 2642\u20132656 (2011).","journal-title":"J. Virol."},{"key":"BFncomms9299_CR15","doi-asserted-by":"publisher","first-page":"5347","DOI":"10.1038\/srep05347","volume":"4","author":"M Krupovic","year":"2014","unstructured":"Krupovic, M. & Koonin, E. V. Evolution of eukaryotic single-stranded DNA viruses of the Bidnaviridae family from genes of four other groups of widely different viruses. Sci. Rep. 4, 5347 (2014).","journal-title":"Sci. Rep."},{"key":"BFncomms9299_CR16","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1745-6150-7-13","volume":"7","author":"GS Diemer","year":"2012","unstructured":"Diemer, G. S. & Stedman, K. M. A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses. Biol. Direct 7, 13 (2012).","journal-title":"Biol. Direct"},{"key":"BFncomms9299_CR17","doi-asserted-by":"publisher","first-page":"e1001191","DOI":"10.1371\/journal.pgen.1001191","volume":"6","author":"A Katzourakis","year":"2010","unstructured":"Katzourakis, A. & Gifford, R. R. J. Endogenous viral elements in animal genomes. PLoS Genet. 6, e1001191 (2010).","journal-title":"PLoS Genet."},{"key":"BFncomms9299_CR18","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/nrg3199","volume":"13","author":"C Feschotte","year":"2012","unstructured":"Feschotte, C. & Gilbert, C. Endogenous viruses: insights into viral evolution and impact on host biology. Nat. Rev. Genet. 13, 283\u2013296 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"BFncomms9299_CR19","doi-asserted-by":"publisher","first-page":"e1001210","DOI":"10.1371\/journal.pgen.1001210","volume":"6","author":"WE Johnson","year":"2010","unstructured":"Johnson, W. E. Endless forms most viral. PLoS Genet. 6, e1001210 (2010).","journal-title":"PLoS Genet."},{"key":"BFncomms9299_CR20","doi-asserted-by":"publisher","first-page":"e1001571","DOI":"10.1371\/journal.pbio.1001571","volume":"11","author":"A Demogines","year":"2013","unstructured":"Demogines, A., Abraham, J., Choe, H., Farzan, M. & Sawyer, S. L. Dual host-virus arms races shape an essential housekeeping protein. PLoS Biol. 11, e1001571 (2013).","journal-title":"PLoS Biol."},{"key":"BFncomms9299_CR21","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1073\/pnas.022629899","volume":"99","author":"S Kumar","year":"2002","unstructured":"Kumar, S. & Subramanian, S. Mutation rates in mammalian genomes. Proc. Natl Acad. Sci. USA 99, 803\u2013808 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms9299_CR22","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/nature01262","volume":"420","author":"RH Waterston","year":"2002","unstructured":"Waterston, R. H. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520\u2013562 (2002).","journal-title":"Nature"},{"key":"BFncomms9299_CR23","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/nature05634","volume":"446","author":"ORP Bininda-Emonds","year":"2007","unstructured":"Bininda-Emonds, O. R. P. et al. The delayed rise of present-day mammals. Nature 446, 507\u2013512 (2007).","journal-title":"Nature"},{"key":"BFncomms9299_CR24","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1093\/molbev\/msm088","volume":"24","author":"Z Yang","year":"2007","unstructured":"Yang, Z. PAML 4: phylogenetic analysis by maximum likelihood. Mol. Biol. Evol. 24, 1586\u20131591 (2007).","journal-title":"Mol. Biol. Evol."},{"key":"BFncomms9299_CR25","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.tree.2012.07.007","volume":"27","author":"A Aswad","year":"2012","unstructured":"Aswad, A. & Katzourakis, A. Paleovirology and virally derived immunity. Trends Ecol. Evol. 27, 627\u2013636 (2012).","journal-title":"Trends Ecol. Evol."},{"key":"BFncomms9299_CR26","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/nrg3098","volume":"12","author":"A Hodgkinson","year":"2011","unstructured":"Hodgkinson, A. & Eyre-Walker, A. Variation in the mutation rate across mammalian genomes. Nat. Rev. Genet. 12, 756\u2013766 (2011).","journal-title":"Nat. Rev. Genet."},{"key":"BFncomms9299_CR27","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/1471-2148-8-53","volume":"8","author":"JJ Welch","year":"2008","unstructured":"Welch, J. J., Bininda-Emonds, O. R. P. & Bromham, L. Correlates of substitution rate variation in mammalian protein-coding sequences. BMC Evol. Biol. 8, 53 (2008).","journal-title":"BMC Evol. Biol."},{"key":"BFncomms9299_CR28","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1177\/117693430700300008","volume":"3","author":"ORP Bininda-Emonds","year":"2007","unstructured":"Bininda-Emonds, O. R. P. Fast genes and slow clades: comparative rates of molecular evolution in mammals. Evol. Bioinform. Online 3, 59\u201385 (2007).","journal-title":"Evol. Bioinform. Online"},{"key":"BFncomms9299_CR29","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1099\/vir.0.80588-0","volume":"86","author":"DJ McGeoch","year":"2005","unstructured":"McGeoch, D. J., Gatherer, D. & Dolan, A. On phylogenetic relationships among major lineages of the Gammaherpesvirinae. J. Gen. Virol. 86, 307\u2013316 (2005).","journal-title":"J. Gen. Virol."},{"key":"BFncomms9299_CR30","doi-asserted-by":"publisher","first-page":"3509","DOI":"10.1128\/JVI.02646-07","volume":"82","author":"B Ehlers","year":"2008","unstructured":"Ehlers, B. et al. Novel mammalian herpesviruses and lineages within the Gammaherpesvirinae: cospeciation and interspecies transfer. J. Virol. 82, 3509\u20133516 (2008).","journal-title":"J. Virol."},{"key":"BFncomms9299_CR31","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1080\/10635150500481390","volume":"55","author":"C Poux","year":"2006","unstructured":"Poux, C., Chevret, P., Huchon, D., de Jong, W. W. & Douzery, E. J. P. Arrival and diversification of caviomorph rodents and platyrrhine primates in South America. Syst. Biol. 55, 228\u2013244 (2006).","journal-title":"Syst. Biol."},{"key":"BFncomms9299_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0014-5793(98)00478-5","volume":"428","author":"ED Sverdlov","year":"1998","unstructured":"Sverdlov, E. D. Perpetually mobile footprints of ancient infections in human genome. FEBS Lett. 428, 1\u20136 (1998).","journal-title":"FEBS Lett."},{"key":"BFncomms9299_CR33","doi-asserted-by":"publisher","first-page":"e5179","DOI":"10.1371\/journal.pone.0005179","volume":"4","author":"F Benachenhou","year":"2009","unstructured":"Benachenhou, F. et al. Evolutionary conservation of orthoretroviral long terminal repeats (LTRs) and ab initio detection of single LTRs in genomic data. PLoS ONE 4, e5179 (2009).","journal-title":"PLoS ONE"},{"key":"BFncomms9299_CR34","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1759-8753-4-5","volume":"4","author":"F Benachenhou","year":"2013","unstructured":"Benachenhou, F. et al. Conserved structure and inferred evolutionary history of long terminal repeats (LTRs). Mob. DNA 4, 5 (2013).","journal-title":"Mob. DNA"},{"key":"BFncomms9299_CR35","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1073\/pnas.89.3.991","volume":"89","author":"R Isfort","year":"1992","unstructured":"Isfort, R., Jones, D., Kost, R., Witter, R. & Kung, H. J. Retrovirus insertion into herpesvirus in vitro and in vivo. Proc. Natl Acad. Sci. USA 89, 991\u2013995 (1992).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms9299_CR36","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.virol.2009.11.017","volume":"397","author":"A-J Sun","year":"2010","unstructured":"Sun, A.-J. et al. Functional evaluation of the role of reticuloendotheliosis virus long terminal repeat (LTR) integrated into the genome of a field strain of Marek\u2019s disease virus. Virology 397, 270\u2013276 (2010).","journal-title":"Virology"},{"key":"BFncomms9299_CR37","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1006\/viro.1997.8691","volume":"235","author":"C Hertig","year":"1997","unstructured":"Hertig, C., Coupar, B. E., Gould, A. R. & Boyle, D. B. Field and vaccine strains of fowlpox virus carry integrated sequences from the avian retrovirus, reticuloendotheliosis virus. Virology 235, 367\u2013376 (1997).","journal-title":"Virology"},{"key":"BFncomms9299_CR38","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/351078a0","volume":"351","author":"BJ Thomson","year":"1991","unstructured":"Thomson, B. J., Efstathiou, S. & Honess, R. W. Acquisition of the human adeno-associated virus type-2 rep gene by human herpesvirus type-6. Nature 351, 78\u201380 (1991).","journal-title":"Nature"},{"key":"BFncomms9299_CR39","doi-asserted-by":"publisher","first-page":"3855","DOI":"10.1073\/pnas.90.9.3855","volume":"90","author":"D Jones","year":"1993","unstructured":"Jones, D., Isfort, R., Witter, R., Kost, R. & Kung, H. J. Retroviral insertions into a herpesvirus are clustered at the junctions of the short repeat and short unique sequences. Proc. Natl Acad. Sci. USA 90, 3855\u20133859 (1993).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms9299_CR40","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.tim.2004.08.005","volume":"12","author":"LA Shackelton","year":"2004","unstructured":"Shackelton, L. A. & Holmes, E. C. The evolution of large DNA viruses: combining genomic information of viruses and their hosts. Trends Microbiol. 12, 458\u2013465 (2004).","journal-title":"Trends Microbiol."},{"key":"BFncomms9299_CR41","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1128\/JVI.01374-08","volume":"83","author":"S Bhadra","year":"2009","unstructured":"Bhadra, S., Lozano, M. & Dudley, J. BALB\/Mtv-null mice responding to strong mouse mammary tumor virus superantigens restrict mammary tumorigenesis. J. Virol. 83, 484\u2013488 (2009).","journal-title":"J. Virol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms9299.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms9299","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms9299.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T10:49:02Z","timestamp":1672915742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms9299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,24]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,11,24]]}},"alternative-id":["BFncomms9299"],"URL":"https:\/\/doi.org\/10.1038\/ncomms9299","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,24]]},"assertion":[{"value":"3 June 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8299"}}