viruses Review Discovery and Further Studies on Giant Viruses at the IHU Mediterranee Infection That Modified the Perception of the Virosphere Clara Rolland 1, Julien Andreani 1, Amina Cherif Louazani 1, Sarah Aherfi 1,3, Rania Francis 1 , 1,2 1, 1 1 Rodrigo Rodrigues , Ludmila Santos Silva y, Dehia Sahmi , Said Mougari , 1 1, 1,2 1,§ 1, Nisrine Chelkha , Meriem Bekliz z, Lorena Silva , Felipe Assis ,Fábio Dornas k, Jacques Yaacoub Bou Khalil 3, Isabelle Pagnier 1,3, Christelle Desnues 1,¶, Anthony Levasseur 1,3, Philippe Colson 1,3,Jônatas Abrahão 1,2 and Bernard La Scola 1,3,* 1 MEPHI, APHM, IRD 198, Aix Marseille Univ, Department of Medicine, IHU-Méditerranée Infection, 13005 Marseille, France; [email protected] (C.R.); [email protected] (J.A.); cherifl[email protected] (A.C.L.); aherfi[email protected] (S.A.); [email protected] (R.F.); [email protected] (R.R.); [email protected] (L.S.S.); [email protected] (D.S.); [email protected] (S.M.); [email protected] (N.C.); [email protected] (M.B.); [email protected] (L.S.); [email protected] (F.A.); [email protected] (F.D.); [email protected] (I.P.); [email protected] (C.D.); [email protected] (A.L.); [email protected] (P.C.); [email protected] (J.A.) 2 Laboratório de Vírus, Instituto de Ciêncas Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Brazil 3 IHU IHU-Méditerranée Infection, 13005 Marseille, France; [email protected] * Correspondence: [email protected] Present address: Institut de Biologie Moléculaire et Cellulaire, CNRS UPR9022, Université de Strasbourg, y 67000 Strasbourg, France. Present address: Stream Biofilm and Ecosystem Research Laboratory, School of Architecture, Civil and z Environmental Engineering (ENAC), Ecole Polytechnique Fed´ érale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. § Present address: Laboratory of emerging phatogens (LEP), Division of Emerging and Transfusion Transmitted Diseases (DETTD), Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), 10903 New Hampshire Ave. Bldg. 52/72, Rm 9586 Silver Spring, MD 20993, USA. Present address: Universidade Federal dos Vales do Jequitinhonha e Mucuri, Code 3910000, Campus JK, k Diamantina, Brazil. ¶ Present address: Aix-Marseille Université, Université de Toulon, CNRS, IRD, MIO UM 110, 13288 Marseille France. Received: 25 February 2019; Accepted: 27 March 2019; Published: 30 March 2019 Abstract: The history of giant viruses began in 2003 with the identification of Acanthamoeba polyphaga mimivirus. Since then, giant viruses of amoeba enlightened an unknown part of the viral world, and every discovery and characterization of a new giant virus modifies our perception of the virosphere. This notably includes their exceptional virion sizes from 200 nm to 2 µm and their genomic complexity with length, number of genes, and functions such as translational components never seen before. Even more surprising, Mimivirus possesses a unique mobilome composed of virophages, transpovirons, and a defense system against virophages named Mimivirus virophage resistance element (MIMIVIRE). From the discovery and isolation of new giant viruses to their possible roles in humans, this review shows the active contribution of the University Hospital Institute (IHU) Mediterranee Infection to the growing knowledge of the giant viruses’ field. Viruses 2019, 11, 312; doi:10.3390/v11040312 www.mdpi.com/journal/viruses Viruses 2019, 11, 312 2 of 28 Keywords: giant virus; amoeba; Mimivirus; virosphere 1. Introduction For this 10th-year anniversary special issue of the journal Viruses, members or former members Viruses 2019, 11, 312 2 of 28 (mostly former PhD) of our team working at the University Hospital Institute (IHU) Mediterranee Infection1. Introduction prepared this review that presents the last 15 years of our work on giant viruses, from the discoveryFor this and 10th-year description anniversary of Mimivirus special issueto our of latestthe journal studies, Viruses, some members under or review former and members others not yet completed.(mostly former PhD) of our team working at the University Hospital Institute (IHU) Mediterranee Infection prepared this review that presents the last 15 years of our work on giant viruses, from the 2. Thediscovery History and of Discoverydescription ofof Mimivirus Giant Viruses to our and latest Their studies, Genetic some under Mobile review Elements and others not yet Ourcompleted. former laboratory, URMITE, a research unit on emerging infectious and tropical diseases, reference center for Rickettsia and rickettsial diseases, was traditionally expert in the isolation and 2. The History of Discovery of Giant Viruses and Their Genetic Mobile Elements study of fastidious and intracellular microorganisms. In the 1990s, we were the first French hospital laboratoryOur to routinelyformer laboratory, identify URMITE, rare bacteria a research using 16Sunit ribosomalon emerging RNA infectious (rRNA) and gene tropical sequencing diseases, [1 ]. In the samereference period, center we for began Rickettsia using and amoebas rickettsial as diseases, cell supports was traditionally for the isolation expert of in intracellularthe isolation and bacteria, study of fastidious and intracellular microorganisms. In the 1990s, we were the first French hospital mostly Legionella, but also as a means to isolate, from human and environmental samples, potential laboratory to routinely identify rare bacteria using 16S ribosomal RNA (rRNA) gene sequencing [1]. new agents responsible for pneumonia that would not grow on axenic culture media [2–8]. Amoeba In the same period, we began using amoebas as cell supports for the isolation of intracellular co-culturebacteria, and mostly identification Legionella, but based also on as thea means 16S rRNAto isolate, sequence from human led usand to environmental collaborate with samples, Dr. Tim Rowbotham,potential thenew scientist agents responsible who described for pneumonia the isolation that ofwouldLegionella not growusing on amoebaaxenic culture co-culture media [ 9[2–8].]; in 1995, a post-doctoralAmoeba co-culture student and from identification his laboratory, based Richard on the 16S Birtles, rRNA came sequence to Marseille led us to to collaborate identify hiswith collection Dr. of amoeba-associatedTim Rowbotham, the bacterial scientist isolates. who described Among the the isolation bacteria of of Legionella this collection, using amoeba mostbeing co-culture identified [9]; as Legionella-in 1995,like a post-doctoral amoebal pathogens student byfrom 16S his rRNA laboratory, gene sequencingRichard Birtles, [10 came], there to Marseille was a small to identify Gram-positive his coccoidcollection bacterium of amoeba-associated provisionally namedbacterial “Bradford isolates. Among coccus”. the bacteria This bacterium of this collection, was later most resistant being to molecularidentified analysis as Legionella- and welike decided amoebal that pathogens examination by 16S rRNA of the gene ultrastructure sequencing of[10], Bradford there was coccus a small using Gram-positive coccoid bacterium provisionally named “Bradford coccus”. This bacterium was later electron microscopy might provide us with a solution to our technical problems, i.e., a particular cell resistant to molecular analysis and we decided that examination of the ultrastructure of Bradford wall thatcoccus would usingprotect electron DNA microscopy from extraction.might provide During us wi examination,th a solution to we our observed technical unexpectedproblems, i.e., regular a icosahedralparticular bodies cell wall that that were would typical protect of a virusDNA butfrom with extraction. the size During of a small examination, bacterium we (Figure observed1). We observedunexpected for the regular first time icosahedral a particle bodies belonging that were to a newtypical group of a ofvirus viruses, but with giant the viruses, size of witha small its first memberbacteriumAcanthamoeba (Figure 1). polyphaga We observed mimivirus for the first(APMV) time a [ 11particle]. Its belonging size of ~600 to a nmnew with group its of surrounding viruses, fibrils,giant the viruses, size of with its genome its first member of 1.2 Mbp, Acanthamoeba and its codingpolyphaga capacity mimivirus including (APMV) [11]. genes Its/ functionssize of ~600 never observednm with in aits virus surrounding let us imagine fibrils, the that size this of its discovery genome of could 1.2 Mbp, deeply and modifyits coding the capacity perception including we had of thegenes/functions virosphere [12 never]. The observed next discoveriesin a virus let us we im madeagine (asthat wellthis discovery as others) could on thedeeply subject modify gradually the confirmedperception this firstwe had impression of the virosphere (Table1). [12]. However, The next at discoveries the stage ofwe this made manuscript, (as well as it others) should on be the noted subject gradually confirmed this first impression (Table 1). However, at the stage of this manuscript, that Mimivirus, seen as a unique circus freak in 2003, is now, 15 years later, one of the most diverse it should be noted that Mimivirus, seen as a unique circus freak in 2003, is now, 15 years later, one of microorganisms,the most diverse at least microorganisms, in sea water at [ 13least]. in sea water [13]. FigureFigure 1.