Widespread human exposure to ledanteviruses in Uganda – a population study

Le Dantec virus (LDV), type species of the genus Ledantevirus within the Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening a cohort of 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to Ledantevirus, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus, Odro virus, in the synanthropic rodent Mastomys erythroleucus . Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by awards from the Wellcome Trust (102789/Z/13/Z and 217221/Z/19/Z) and the MRC (MC\_UU\_12014/8 and MC\_ST\_U17020). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research ethics committee of the Uganda Virus Research Institute (UVRI) gave ethical approval for this work (reference numbers GC/127/10/02/19, GC/127/18/09/662 and GC/127/19/06/662). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Consensus viral genome and mitochondrial cytochrome B sequences have been submitted to GenBank under accession numbers [OQ077988][1], [OR497399][2] and [OR607590][3]. Raw sequencing read files derived from rodent blood have been submitted to NCBI sequence read archive (BioProject ID PRJNA1013481, Biosample accession SAMN37299165). Experimental data relating to LEDV-ELISA and pseudotype-based neutralisation assays will be made available on request to the authors. [1]: /lookup/external-ref?link_type=GEN&access_num=OQ077988&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F02%2F2023.09.29.23296156.atom [2]: /lookup/external-ref?link_type=GEN&access_num=OR497399&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F02%2F2023.09.29.23296156.atom [3]: /lookup/external-ref?link_type=GEN&access_num=OR607590&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F02%2F2023.09.29.23296156.atom