Molecular Characterization of Complete Simian Foamy Virus Genomes from Three Colobine Monkeys Reveals Highly Divergent Evolutionary Trajectories and Identifies Transmission to Humans

Simian foamy viruses (SFVs) are ancient retroviruses that co-evolve with nonhuman primates (NHPs), although genomic data from Asian and African monkeys are limited. We report the characterization of three new SFV colobine genomes from two Asian species (<i>Trachypithecus francoisi</i> (Tfr) and <i>Pygathrix nemaeus</i> (Pne)) and one African monkey (<i>Colobus guereza</i>, Cgu), obtained via metagenomics analysis of peripheral blood leukocyte tissue culture isolates. Genomic analyses found conserved structural, enzymatic, and auxiliary genes flanked by long terminal repeats, with all major transcriptional and structural motifs highly preserved. An in-frame Δtas mutation in tissue culture and ex vivo specimens was identified in the SFVpne genome, which may promote viral latency. Phylogenetic analyses revealed that these colobine SFVs have distinct evolutionary trajectories without clustering together, contradicting a strict virus-host co-evolution. We developed a new generic SFV PCR assay using these genomes with increased detection sensitivity for Colobinae SFVs and identified four new human infections with Cgu-derived SFV in the Democratic Republic of Congo. Our findings indicate that SFV evolution in colobine monkeys is shaped by host switching, cross-species transmission, and high viral diversity. Our study underscores the importance of broadening SFV genomic sampling to better understand viral evolution, zoonotic risk, and improved diagnostic capabilities.