{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:32:28Z","timestamp":1787970748875,"version":"build-2784847793"},"reference-count":31,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"St Vincent Health Care Group of Dublin"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Mimiviruses or giant viruses that infect amoebas have the ability to retain the Gram stain, which is usually used to colour bacteria. There is some evidence suggesting that Mimiviruses can also infect human cells. Guided by these premises, we performed a routine Gram stain on a variety of human specimens to see if we could detect the same Gram positive blue granules that identify Mimiviruses in the amoebas.\u00a0\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    We analysed 24 different human specimens (liver, brain, kidney, lymph node and ovary) using Gram stain histochemistry, electron microscopy immunogold, high resolution mass spectrometry and protein identification.\u00a0\n                    <ns4:bold>Results:<\/ns4:bold>\n                    We detected in the human cells Gram positive granules that were distinct from bacteria. The fine blue granules displayed the same pattern of the Gram positive granules that diagnose Mimiviruses in the cytoplasm of the amoebas. Electron microscopy confirmed the presence of human Mimiviruses-like structures and mass spectrometry identified histone H4 peptides, which had the same footprints as giant viruses. However, some differences were noted: the Mimivirus-like structures identified in the human cells were ubiquitous and manifested a distinct mammalian retroviral antigenicity.\u00a0\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Our main hypotheses are that the structures could be either giant viruses having a retroviral antigenicity or ancestral cellular\u00a0components having a viral origin.\u00a0However, other possible alternatives have been proposed to explain the nature and function\u00a0of the newly identified structures.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.11007.1","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T06:10:04Z","timestamp":1489471804000},"page":"262","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Questions on unusual Mimivirus-like structures observed in human cells"],"prefix":"10.12688","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-7410","authenticated-orcid":false,"given":"Elena Angela","family":"Lusi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Maloney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-449X","authenticated-orcid":false,"given":"Federico","family":"Caicci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-4451","authenticated-orcid":false,"given":"Paolo","family":"Guarascio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2017,3,14]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"e225-34","DOI":"10.1016\/S1473-3099(16)30051-2","article-title":"Marseillevirus in Lymphoma: a giant in the lymph node.","volume":"16","author":"S Aherfi","year":"2016","journal-title":"Lancet Infect Dis."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"199-208","DOI":"10.1016\/j.mib.2016.04.012","article-title":"The role of giant viruses of amoebas in humans.","volume":"31","author":"P Colson","year":"2016","journal-title":"Curr Opin Microbiol."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"376-85","DOI":"10.1159\/000354558","article-title":"Giant viruses of amoebae as potential human pathogens.","volume":"56","author":"P Colson","year":"2013","journal-title":"Intervirology."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"95-102","DOI":"10.1086\/518608","article-title":"The discovery and characterization of Mimivirus, the largest known virus and putative pneumonia agent.","volume":"45","author":"D Raoult","year":"2007","journal-title":"Clin Infect Dis."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"111-8","DOI":"10.1080\/bih.76.3.111.118","article-title":"Use of the gram stain in microbiology.","volume":"76","author":"T Beveridge","year":"2001","journal-title":"Biotech Histochem."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1126\/science.1081867","article-title":"A giant virus in amoebae.","volume":"299","author":"B La Scola","year":"2003","journal-title":"Science."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"485-493","DOI":"10.3109\/10520295.2012.687117","article-title":"Energy filtering transmission electron microscopy immunocytochemistry and antigen retrieval of surface layer proteins from Tannerella forsythensis using microwave or autoclave heating with citraconic anhydride.","volume":"87","author":"K Moriguchi","year":"2012","journal-title":"Biotech Histochem."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"77-81","DOI":"10.3109\/00313020903434439","article-title":"Citraconic anhydride: a new antigen retrieval solution.","volume":"42","author":"A Leong","year":"2010","journal-title":"Pathology."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"264-75","DOI":"10.1038\/nrm2861","article-title":"Histone variants--ancient wrap artists of the epigenome.","volume":"11","author":"P Talbert","year":"2010","journal-title":"Nat Rev Mol Cell Biol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"295-310","DOI":"10.1101\/gad.1272805","article-title":"Histone variants: deviants?","volume":"19","author":"R Kamakaka","year":"2005","journal-title":"Genes Dev."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"271-77","DOI":"10.1016\/j.virol.2015.03.041","article-title":"Plants, Viruses and the environment: Ecology and mutualism.","volume":"479\u2013480","author":"M Roossinck","year":"2015","journal-title":"Virology."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"95-102","DOI":"10.1046\/j.1365-2893.2003.00417.x","article-title":"TT virus has a ubiquitous diffusion in human body tissues: analyses of paired serum and tissue samples.","volume":"10","author":"T Pollicino","year":"2003","journal-title":"J Viral Hepat."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"337-9","DOI":"10.1002\/rmv.1761","article-title":"Orphan viruses, orphan diseases: still the raw material for virus discovery.","volume":"23","author":"P Mortimer","year":"2013","journal-title":"Rev Med Virol."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"277-89","DOI":"10.1016\/j.bbagrm.2011.09.007","article-title":"Histone chaperones link histone nuclear import and chromatin assembly.","volume":"1819","author":"K Keck","year":"2013","journal-title":"Bioch Biophys Acta."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"357-63","DOI":"10.1042\/BST20110737","article-title":"Histone transfer among chaperones.","volume":"40","author":"W Liu","year":"2012","journal-title":"Biochem Soc 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Andersson","year":"2003","journal-title":"Philos Trans R Soc Lond B Biol Sci."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"1454-66","DOI":"10.1111\/j.1462-2920.2011.02446.x","article-title":"Lausannevirus, a giant amoebal virus encoding histone doublets.","volume":"13","author":"V Thomas","year":"2011","journal-title":"Environ Microbiol."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"931-8","DOI":"10.1099\/vir.0.83585-0","article-title":"A viral histone H4 encoded by Cotesia plutellae bracovirus inhibits haemocyte-spreading behaviour of the diamondback moth, Plutella xylostella.","volume":"89","author":"W Gad","year":"2008","journal-title":"J Gen Virol."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"11223-30","DOI":"10.1128\/JVI.01759-13","article-title":"A viral histone h4 joins to eukaryotic nucleosomes and alters host gene expression.","volume":"87","author":"R Hepat","year":"2013","journal-title":"J Virol."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12985-015-0400-7","article-title":"Viruses and cells intertwined since the dawn of evolution.","volume":"12","author":"J Durzy\u0144ska","year":"2015","journal-title":"Virol J."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"58-62","DOI":"10.1016\/j.coviro.2011.05.008","article-title":"Giant viruses in the environment: their origins and evolution.","volume":"1","author":"T Yamada","year":"2011","journal-title":"Curr Opin Virol."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"20140327","DOI":"10.1098\/rstb.2014.0327","article-title":"Evolution of viruses and cells: do we need a fourth domain of life to explain the origin of eukaryotes?","volume":"370","author":"D Moreira","year":"2015","journal-title":"Philos Trans R Soc Lond B Sci."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"44-9","DOI":"10.1016\/j.mib.2016.02.001","article-title":"Giant viruses and the origin of modern eukaryotes.","volume":"31","author":"P Forterre","year":"2016","journal-title":"Curr Opin Microbiol."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"95-106","DOI":"10.1016\/0014-4827(69)90462-5","article-title":"Studies on induced cellular autophagy. I. Electron microscopy of cells with in vivo labelled lysosomes.","volume":"55","author":"J Ericsson","year":"1969","journal-title":"Exp Cell Res."},{"key":"ref-28","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1136\/bmj.1.3396.221-c","article-title":"Professor Camillo Golgi.","volume":"1","year":"1926","journal-title":"Br Med J."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"3732-7","DOI":"10.1016\/j.febslet.2009.10.018","article-title":"How Camillo Golgi became \"the Golgi\".","volume":"583","author":"P Mazzarello","year":"2009","journal-title":"FEBS Lett."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"241-7","DOI":"10.1007\/BF02427612","article-title":"One hundred years of the Golgi apparatus: history of a disputed cell organelle.","volume":"19","author":"M Bentivoglio","year":"1998","journal-title":"Ital J Neurol Sci."},{"key":"ref-31","doi-asserted-by":"publisher","DOI":"10.5256\/f1000research.11007.d153802","article-title":"Dataset 1 in: Questions on unusual Mimivirus-like structures observed in human cells.","author":"E Lusi","year":"2017","journal-title":"F1000Research."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/6-262\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/6-262\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/6-262\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T10:25:12Z","timestamp":1544091912000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/6-262\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,14]]},"references-count":31,"URL":"https:\/\/doi.org\/10.12688\/f1000research.11007.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.11867.r21292","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.11867.r20949","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.11867.r21292","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.11867.r20949","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,14]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/6-262\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.11867.r20949, Carlo Presutti, Milena Grossi, Dep. Biology and Biotechnology, University of Rome, Rome, 00185, Italy, 25 May 2017, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/6-262\/v1#referee-response-20949","order":0,"name":"referee-response-20949","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Elena Angela Lusi<\/b>; \n<i>Posted: 26 Sep 2017<\/i>; Author ResponseMy previous report of unusual Mimiviruses-like structures in human cells required additional investigations. This time I will focus on clarifying their unique retroviral nature.&nbsp;With a pan retroviral-PCR detection system (1) and genomic sequencing, I can be quite confident in stating that the mimivirus-like structures \n<b>are human <u>Retro<\/u>-Giant-Viruses.&nbsp; &nbsp;<\/b>The retroviral sequences identified showed \u226590% nucleotide identity to the HERV-W species of human endogenous retroviruses (sequence deposited in GenBank with the accession number BankIt2050100 BSeq#1&nbsp;MF996371).&nbsp;This genetic analysis further confirms the &nbsp;already described EM tests where an anti FeLV p27gag MoAb \n<u>specifically marked the giant viruses as well as the viral factory<\/u>, (refer to the\n<i>&nbsp;striking EM immunogold image&nbsp;&nbsp;with an anti Feline Leukemia virus protein p27gag, black dots).<\/i>&nbsp;In fact, the \n<i>pol<\/i> genes of the viruses HERV-W are all related to other mammalian C-type retroviruses, such as murine leukemia virus, gibbon ape leukemia virus, and feline leukemia virus, on the basis of nucleotide and amino acid sequence homology (2-7).We are facing not an archetypal human retrovirus nor even a large human retrovirus, but a human giant virus with an ancestral mammalian retroviral core.Although sharing some morphological features with Mimiviruses, this human Retro-giant virus differ substantially from the DNA-amoebal giant viruses for its unique presence of mammalian retroviral genes (gag, &nbsp;pol and env).I believe that this finding will add a new dimension to the giant viruses in general and challenge our current concepts in retrovirology. The old classification and taxonomy of retroviruses&nbsp; might&nbsp; need an update and should include the Retro-giant viruses.&nbsp;&nbsp;Elena Angela Lusi M.D., Ph.D.St Vincent Health Care Group-UCD, Dublin, Ireland.\n<b>&nbsp;Suggested References <\/b>  Tuke PW, Perron H, Bedin F, Beseme F, Garson JA. &nbsp;Development of a pan-retrovirus detection system for multiple sclerosis studies. \n<i>Acta Neurol Scand<\/i> Suppl. 1997;169:16-21. Sherr C. J., Fedele L. A., Benveniste R. E., Todaro G. J. , Interspecies antigenic determinants of the reverse transcriptases and p30 proteins of mammalian type C viruses. \n<i>J Virol<\/i>. 15(6), 1440-8 (1975) M. A. Morgan, T. D. Copeland, S. Oroszlan, Structural and antigenic analysis of the nucleic acid-binding proteins of bovine and feline leukemia viruses. \n<i>J Virol.<\/i> 46(1), 177-86 (1983) G. Geering, T. Aoki, L. J. Old, Shared viral antigen of mammalian leukaemia viruses. \n<i>Nature.<\/i> 226(5242),265\u2013266 (1970) J. Davis, R. V. Gilden , S. Oroszlan, Multiple species-specific and interspecific antigenic determinants of a mammalian type C RNA virus internal protein. \n<i>Immunochemistry<\/i> 12(1), 67-72 (1975) &nbsp;Blond J-L, Bes&egrave;me F, Duret L, Bouton O, Bedin F, Perron H, Mandrand B, Mallet F. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. \n<i>J Virol<\/i>. 1999;73:1175\u20131185. M. Wunsch, A. S. Schulz, W. Kock, R. Friedrich, G. Hunsmann, Sequence analysis of Gardner-Arnstein feline leukaemia virus envelope gene reveals common structural properties of mammalian retroviral envelope genes. \n<i>EMBO J.<\/i> 2(12), 2239\u20132246 (1983)&nbsp;","URL":"https:\/\/f1000research.com\/articles\/6-262\/v1#referee-comment-3062","order":1,"name":"referee-comment-3062","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.11867.r21292, Didier Raoult, Institut Hospitalo-Universitaire M\u00e9diterran\u00e9e-Infection,  Facult\u00e9 de m\u00e9decine, Aix-Marseille Universit\u00e9, URMITE, UM63, CNRS7278, IRD198, Inserm 1095, Marseille, France, 12 Jun 2017, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/6-262\/v1#referee-response-21292","order":2,"name":"referee-response-21292","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Elena Angela Lusi<\/b>; \n<i>Posted: 26 Sep 2017<\/i>; Author ResponseMy previous report of unusual Mimiviruses-like structures in human cells required additional investigations. This time I will focus on clarifying their unique retroviral nature.&nbsp;With a pan retroviral-PCR detection system (1) and genomic sequencing, I can be quite confident in stating that the mimivirus-like structures \n<b>are human <u>Retro<\/u>-Giant-Viruses.&nbsp; &nbsp;<\/b>The retroviral sequences identified showed \u226590% nucleotide identity to the HERV-W species of human endogenous retroviruses (sequence deposited in GenBank with the accession number BankIt2050100 BSeq#1&nbsp;MF996371).&nbsp;This genetic analysis further confirms the &nbsp;already described EM tests where an anti FeLV p27gag MoAb \n<u>specifically marked the giant viruses as well as the viral factory<\/u>, ( refer to the\n<i>&nbsp;striking EM immunogold image&nbsp;&nbsp;with an anti Feline Leukemia virus protein p27gag, black dots .)<\/i>In fact, the \n<i>pol<\/i> genes of the viruses HERV-W are all related to other mammalian C-type retroviruses, such as murine leukemia virus, gibbon ape leukemia virus, and feline leukemia virus, on the basis of nucleotide and amino acid sequence homology (2-7).We are facing not an archetypal human retrovirus nor even a large human retrovirus, but a human giant virus with an ancestral mammalian retroviral core.Although sharing some morphological features with Mimiviruses, this human Retro-giant virus differ substantially from the DNA-amoebal giant viruses for its unique presence of mammalian retroviral genes (gag, &nbsp;pol and env).I believe that this finding will add a new dimension to the giant viruses in general and challenge our current concepts in retrovirology. The old classification and taxonomy of retroviruses&nbsp; might&nbsp; need an update and should include the Retro-giant viruses.&nbsp;&nbsp;Elena Angela Lusi M.D., Ph.D.St Vincent Health Care Group-UCD, Dublin, Ireland.\n<b>&nbsp;Suggested References <\/b>  Tuke PW, Perron H, Bedin F, Beseme F, Garson JA. &nbsp;Development of a pan-retrovirus detection system for multiple sclerosis studies. \n<i>Acta Neurol Scand<\/i> Suppl. 1997;169:16-21. Sherr C. J., Fedele L. A., Benveniste R. E., Todaro G. J. , Interspecies antigenic determinants of the reverse transcriptases and p30 proteins of mammalian type C viruses. \n<i>J Virol<\/i>. 15(6), 1440-8 (1975) M. A. Morgan, T. D. Copeland, S. Oroszlan, Structural and antigenic analysis of the nucleic acid-binding proteins of bovine and feline leukemia viruses. \n<i>J Virol.<\/i> 46(1), 177-86 (1983) G. Geering, T. Aoki, L. J. Old, Shared viral antigen of mammalian leukaemia viruses. \n<i>Nature.<\/i> 226(5242),265\u2013266 (1970) J. Davis, R. V. Gilden , S. Oroszlan, Multiple species-specific and interspecific antigenic determinants of a mammalian type C RNA virus internal protein. \n<i>Immunochemistry<\/i> 12(1), 67-72 (1975) &nbsp;Blond J-L, Bes&egrave;me F, Duret L, Bouton O, Bedin F, Perron H, Mandrand B, Mallet F. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. \n<i>J Virol<\/i>. 1999;73:1175\u20131185. M. Wunsch, A. S. Schulz, W. Kock, R. Friedrich, G. Hunsmann, Sequence analysis of Gardner-Arnstein feline leukaemia virus envelope gene reveals common structural properties of mammalian retroviral envelope genes. \n<i>EMBO J.<\/i> 2(12), 2239\u20132246 (1983)&nbsp;","URL":"https:\/\/f1000research.com\/articles\/6-262\/v1#referee-comment-3061","order":3,"name":"referee-comment-3061","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the St Vincent Health Care Group of Dublin.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}