title: Sequences of flavivirus-related RNA viruses persist in DNA form integrated in the genome of Aedes spp. mosquitoes.
abstract: Flavivirus-related sequences have been discovered in the dsDNA genome of Aedes albopictus and Aedes aegypti mosquitoes, demonstrating for the first time an integration into a eukaryotic genome of a multigenic sequence from an RNA virus that replicates without a recognized DNA intermediate. In the Aedes albopictus C6/36 cell line, an open reading frame (ORF) of 1557 aa with protease/helicase and polyprotein processing domains characteristic of flaviviruses was identified. It is closely related to NS1-NS4A genes of the Cell Fusing Agent and Kamiti River virus and the corresponding mRNAs were detected. Integrated sequences homologous to the envelope, NS4B and polymerase genes of flaviviruses were identified. Overall, approximately two-thirds of a flavivirus-like genome were characterized. In the Aedes aegypti A20 cell line, a 492 aa ORF related to the polymerase of the Cell Fusing Agent and Kamiti River virus was identified. These flavivirus-related integrated DNA sequences were detected in laboratory-bred and wild Aedes albopictus and Aedes aegypti mosquitoes, demonstrating that their discovery is not an artefact resulting from the manipulation of mosquito cell lines, since they exist under natural conditions. This finding has major implications regarding evolution, as it represents an entirely different mechanism by which genetic diversity may be generated in eukaryotic cells distinct from accepted processes.
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Crochu
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
authors.forename: Shelley
authors.initials: S
authors.lastname: Cook
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Houssam
authors.initials: H
authors.lastname: Attoui
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Remi N
authors.initials: RN
authors.lastname: Charrel
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Reine
authors.initials: R
authors.lastname: De Chesse
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Mourad
authors.initials: M
authors.lastname: Belhouchet
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lemasson
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: de Micco
authors.affiliation: Unité des Virus Emergents, Faculté de Médecine de Marseille, IFR48-IRD UR034, 27 boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: de Lamballerie
mesh_terms: D000330:Aedes / Q000145:classification / Q000821:virology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D005416:Flavivirus / Q000145:classification* / Q000235:genetics*; D016679:Genome, Viral; D008969:Molecular Sequence Data; D010802:Phylogeny; D012328:RNA Viruses / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016662:Virus Integration / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D012333:RNA, Messenger