Ecuador Paraiso Escondido Virus, a New Flavivirus Isolated from New World Sand Flies in Ecuador, Is the First Representative of a Novel Clade in the Genus Flavivirus.
A new flavivirus, Ecuador Paraiso Escondido virus (EPEV), named after the village where it was discovered, was isolated from sand flies (Psathyromyia abonnenci, formerly Lutzomyia abonnenci) that are unique to the New World. This represents the first sand fly-borne flavivirus identified in the New World. EPEV exhibited a typical flavivirus genome organization. Nevertheless, the maximum pairwise amino acid sequence identity with currently recognized flaviviruses was 52.8%. Phylogenetic analysis of the complete coding sequence showed that EPEV represents a distinct clade which diverged from a lineage that was ancestral to the nonvectored flaviviruses Entebbe bat virus, Yokose virus, and Sokoluk virus and also the Aedes-associated mosquito-borne flaviviruses, which include yellow fever virus, Sepik virus, Saboya virus, and others. EPEV replicated in C6/36 mosquito cells, yielding high infectious titers, but failed to reproduce either in vertebrate cell lines (Vero, BHK, SW13, and XTC cells) or in suckling mouse brains. This surprising result, which appears to eliminate an association with vertebrate hosts in the life cycle of EPEV, is discussed in the context of the evolutionary origins of EPEV in the New World.


OBJECTIVE
The flaviviruses are rarely (if ever) vectored by sand fly species, at least in the Old World. We have identified the first representative of a sand fly-associated flavivirus, Ecuador Paraiso Escondido virus (EPEV), in the New World. EPEV constitutes a novel clade according to current knowledge of the flaviviruses. Phylogenetic analysis of the virus genome showed that EPEV roots the Aedes-associated mosquito-borne flaviviruses, including yellow fever virus. In light of this new discovery, the New World origin of EPEV is discussed together with that of the other flaviviruses.
Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France IHU Mediterranée Infection, APHM Public Hospitals of Marseille, Marseille, France cgdmalkan@gmail.com remi.charrel@univ-amu.fr.
Cigdem
C
Alkan
Instituto de Microbiología, Universidad San Francisco de Quito, Quito, Ecuador.
Sonia
S
Zapata
Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France IHU Mediterranée Infection, APHM Public Hospitals of Marseille, Marseille, France.
Laurence
L
Bichaud
Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France IHU Mediterranée Infection, APHM Public Hospitals of Marseille, Marseille, France.
Grégory
G
Moureau
Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
Philippe
P
Lemey
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Andrew E
http://orcid.org/0000-0002-7986-9520
AE
Firth
School of Biological Sciences, University of Reading, Whiteknights, Reading, United Kingdom.
Tamara S
TS
Gritsun
Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France IHU Mediterranée Infection, APHM Public Hospitals of Marseille, Marseille, France.
Ernest A
EA
Gould
Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France IHU Mediterranée Infection, APHM Public Hospitals of Marseille, Marseille, France.
Xavier
X
de Lamballerie
Université de Reims Champagne-Ardenne, ANSES, EA 4688 USC VECPAR Transmission Vectorielle et Épidémiosurveillance de Maladies Parasitaires, SFR Capsanté, Reims, France.
Jérôme
J
Depaquit
Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France IHU Mediterranée Infection, APHM Public Hospitals of Marseille, Marseille, France cgdmalkan@gmail.com remi.charrel@univ-amu.fr.
Rémi N
RN
Charrel
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D001921:Brain / Q000821:virology; D002460:Cell Line; D016000:Cluster Analysis; D004484:Ecuador; D005416:Flavivirus / Q000145:classification* / Q000235:genetics* / Q000502:physiology; D016679:Genome, Viral / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D011576:Psychodidae / Q000821:virology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013045:Species Specificity; D014779:Virus Replication / Q000502:physiology