Climate and land-use shape the spread of zoonotic yellow fever virus

Zoonotic viruses that originate in wildlife harm global human health and economic prosperity[1][1]. Understanding virus transmission at the human-animal-environment interface is a key component of pandemic risk-reduction[2][2],[3][3]. Zoonotic disease emergence is highest in biodiverse, tropical forests undergoing intensive land-use change[4][4],[5][5]. Phylodynamic analyses of virus genomes can powerfully test epidemiological hypotheses, but are rarely applied to viruses of animals inhabiting these habitats. Brazil’s densely-populated Atlantic Forest and Cerrado region experienced in 2016–2021 an explosive human outbreak of sylvatic yellow fever, caused by repeated virus spillover from wild neotropical primates[6][6]. Here we use yellow fever virus (YFV) genome sequences and epidemiological data from neotropical primates, humans, and mosquito vectors to identify the environmental, demographic, and climatic factors determining zoonotic virus spread. Using portable sequencing approaches we generated 498 YFV genomes, resulting in a well-sampled dataset of zoonotic virus genomes sampled from wild mammals. YFV dispersal velocity was slower at higher elevation, in colder regions, and further away from main roads. Virus lineage dispersal was more frequent through wetter areas, areas with high neotropical primate density and through landscapes covered by mosaic vegetation. Higher temperatures were associated with higher virus effective population sizes, and peaks of transmission in warmer, wetter seasons were associated with higher virus evolutionary rates. Our study demonstrates how zoonotic disease transmission is linked to land-use and climate, underscoring the need for One-Health approaches to reducing the rate of zoonotic spillover. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by a Medical Research Council-São Paulo Research Foundation (FAPESP) CADDE partnership award (MR/S0195/1 and FAPESP 18/14389-0) (). SCH was supported by a Sir Henry Wellcome Postdoctoral Fellowship (220414/Z/20/Z). IMC was supported by FAPESP Doctoral Fellowship (2018/17176-8). SD acknowledges support from the Fonds National de la Recherche Scientifique (F.R.S.-FNRS, Belgium; grant no. F.4515.22), from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, FWO, Belgium; grant no. G098321N), and from the European Union Horizon 2020 project MOOD (grant agreement no. 874850).The Flavivirus Laboratory at Fiocruz is grateful for the support received from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro /Faperj (grant number E-26/202.930/2016) and by the Coordenação de Vigilância em Saúde e e Laboratórios de Referência da Fundação Oswaldo Cruz / Ministério da Saúde do Brasil. GRWW was funded by the MOOD H2020 Project 874850. OJB was supported by a UK Medical Research Council Career Development Award (MR/V031112/1). AEZ and OGP are supported by The Oxford Martin School Programme on Pandemic Genomics (). GB acknowledges support from the Internal Funds KU Leuven (Grant No. C14/18/094) and the Research Foundation-Flanders (Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, G0E1420N, G098321N). PL acknowledges the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z - ARTIC network), the European Research Council (grant agreement no. 725422 - ReservoirDOCS) and NIH grant R01AI153044. NRF was supported by a Sir Henry Dale Wellcome Trust Fellowship (204311/Z/16/Z). We also gratefully acknowledge support from Oxford Nanopore Technologies for a donation of sequencing reagents. ### 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: Research at Fundação Oswaldo Cruz in Rio de Janeiro (Fiocruz) and Fundação Ezequiel Dias in Minas Gerais (Funed) was supported by the Pan American Health Organization (PAHO) and the Brazilian Ministry of Health as part of arboviral surveillance efforts according to Resolution 510/2016 of the National Ethical Committee for Research (Comissão Nacional de Ética em Pesquisa; CONEP). Yellow fever virus (YFV) genomic diagnostics on residual human diagnostic samples was approved by the Ethics Committee of the Oswaldo Cruz Institute (CAAE90249218.6.1001.54248). Genomic surveillance of neotropical primate carcasses by Instituto Adolf Lutz in São Paulo (IAL) was approved by the IAL Ethics Committee for Animal Use in Research (0135D/2012 and 020G/2014). Research on residual, anonymised human samples obtained by IAL was supported by the Brazilian Ministry of Health as part of arboviral genomic surveillance efforts according to Resolution 510/2016 of CONEP (National Ethical Committee for Research, Ministry of Health). Research on residual, anonymised human samples collected at Hospital das Clínicas and sequenced at Instituto de Medicina Tropical (IMT), Universidade de São Paulo, São Paulo (IMT-USP) was approved by the HC-FMUSP Ethics in Research Committee (#2.669.963, #3.258.615, and #3.371.745). 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All newly generated sequences are deposited on GenBank, with accession numbers [ON022238][7] - [ON022746][8]. XML code for phylodynamic analyses is available in Data S19. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4 [5]: #ref-5 [6]: #ref-6 [7]: /lookup/external-ref?link_type=GEN&access_num=ON022238&atom=%2Fmedrxiv%2Fearly%2F2022%2F08%2F26%2F2022.08.25.22278983.atom [8]: /lookup/external-ref?link_type=GEN&access_num=ON022746&atom=%2Fmedrxiv%2Fearly%2F2022%2F08%2F26%2F2022.08.25.22278983.atom