title: Discovery of novel rhabdoviruses in the blood of healthy individuals from West Africa.
abstract: Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen's nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.
authors.affiliation: FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Stremlau
authors.affiliation: FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Kristian G
authors.initials: KG
authors.lastname: Andersen
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; Department of Biological Sciences, College of Natural Sciences, Redeemer's University, Redemption City, Ogun State, Nigeria.
authors.forename: Onikepe A
authors.initials: OA
authors.lastname: Folarin
authors.affiliation: Department of Microbiology and Immunology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Grove
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: Ikponmwonsa
authors.initials: I
authors.lastname: Odia
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: Philomena E
authors.initials: PE
authors.lastname: Ehiane
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: Omowunmi
authors.initials: O
authors.lastname: Omoniwa
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: Omigie
authors.initials: O
authors.lastname: Omoregie
authors.affiliation: FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Jiang
authors.affiliation: FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Yozwiak
authors.affiliation: Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Matranga
authors.affiliation: Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Gire
authors.affiliation: FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Winnicki
authors.affiliation: Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Ridhi
authors.initials: R
authors.lastname: Tariyal
authors.affiliation: Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: Peter O
authors.initials: PO
authors.lastname: Okokhere
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: Sylvanus
authors.initials: S
authors.lastname: Okogbenin
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: George O
authors.initials: GO
authors.lastname: Akpede
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Asogun
authors.affiliation: Lahor Research Laboratories and Medical Centre, Benin City, Edo State, Nigeria.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Agbonlahor
authors.affiliation: CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratory, Geelong, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Walker
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Tesh
authors.affiliation: Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Levin
authors.affiliation: Department of Microbiology and Immunology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Garry
authors.affiliation: FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America; Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
authors.affiliation: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; Department of Biological Sciences, College of Natural Sciences, Redeemer's University, Redemption City, Ogun State, Nigeria.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Happi
mesh_terms: D000328:Adult; D000354:Africa, Western / Q000453:epidemiology; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009549:Nigeria / Q000453:epidemiology; D012328:RNA Viruses / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D012367:RNA, Viral / Q000235:genetics*; D012209:Rhabdoviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D018353:Rhabdoviridae Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology*; D017423:Sequence Analysis, RNA
chemical_list: D012367:RNA, Viral