Characterization of the first complete genome sequence of yellow fever virus (YFV) in Sierra Leone: Implications for public health

Abstract

Yellow fever virus (YFV), a mosquito-borne orthoflavivirus that causes severe hemorrhagic disease, is endemic in parts of South America and Africa, yet genomic data from Sierra Leone is lacking despite ongoing case-based surveillance. Using hybrid-capture metagenomic sequencing, we generated a complete 10,611 nt YFV genome (98% coverage) from an adult male patient who reported to the Kailahun Government Hospital with fever and muscle pain. Phylogenetic analysis assigned the genome to the West African II genotype via the YFV Nextstrain build. The Sierra Leone genome showed 57 substitutions, three of which were non-synonymous (NS2B: N79S, NS3: V515I, and NS5 (RdRp domain): A643V), relative to its most recent common ancestor with other genomes from Senegal and the Netherlands. Bayesian phylogenetics estimated the time to the most recent common ancestor with these genomes as January 14, 2001 (95% HPD: December 17, 1987 - April 28, 2009), potentially indicative of long-standing transmission within West Africa that has not been genomically characterized, rather than specific localization to Sierra Leone. Together, these findings underscore the need for expanded genomic surveillance to monitor YFV spread and evolution.