Genomic Insights into Neglected Orthobunyaviruses: Molecular Characterization and Phylogenetic Analysis

Abstract

Orthobunyaviruses are a diverse group of segmented RNA viruses with significant but underexplored public and veterinary health implications. This study provides a genomic, phylogenetic, and ecological analysis of neglected Orthobunyaviruses using next-generation sequencing and computational predictions. We identified unique phylogenetic relationships, with Tanga virus forming a distinct lineage linked to zoonotic, human-associated, or non-vertebrate viruses across segments. GC content analysis revealed segment-specific patterns: higher GC content in the S segment suggests genomic stability and immune evasion, while lower GC content in the L segment reflects host-vector adaptation. Phylogenetic ties to well-characterized pathogenic viruses, such as Ilesha virus with Cache Valley virus and Bwamba virus with California encephalitis virus, indicate potential neurotropism. Ingwavuma virus clustered with Oropouche virus, suggesting risks of systemic febrile illnesses. Within the Simbu serogroup, Sango and Sabo viruses show teratogenic risks to livestock. Vector and host predictions implicate rodents, artiodactyls, and primates in Orthobunyavirus transmission, emphasizing complex ecological dynamics and zoonotic potential. These findings advance the understanding of Orthobunyavirus diversity, linking genomic features to pathogenicity and ecological adaptation, while providing a foundation for future surveillance and intervention strategies targeting these neglected viruses.

Keywords: genomic characterization; neglected Orthobunyaviruses; phylogenetics; vector-borne diseases; zoonotic potential.

Figure 1

Segment-specific GC content patterns across Orthobunyavirus strains. Insights into genomic stability and evolutionary pressures, highlighting higher GC content in S segments and variability in L segments.

Figure 2

Coverage depth of Orthobunyavirus genomic segments. Variation in sequencing depth across strains and segments, emphasizing regions with higher sequencing quality and robustness.

Figure 3

Phylogenetic relationships of Orthobunyaviruses across genomic segments. Maximum-likelihood phylogenetic trees for L, M, and S segments, revealing evolutionary ties to well-characterized pathogenic viruses. Each segment was assessed independently to explore genetic diversity and phylogenetic positioning. Bootstrap values indicate the confidence of clustering, with reference sequences from known Orthobunyaviruses included for comparison. Strains analyzed in this study are highlighted in red, showing their placement within the broader Orthobunyavirus phylogeny. Branch colors indicate virus associations: yellow for human-associated viruses, green for zoonotic viruses, and blue for non-vertebrate-associated viruses.

Figure 4

Predicted reservoir hosts of neglected Orthobunyaviruses using viral host predictor (VHP). High-confidence predictions of primary reservoir hosts, emphasizing roles of rodents, artiodactyls, and primates.

Figure 5

Predicted arthropod vectors of neglected Orthobunyaviruses using viral host predictor (VHP). Predicted vector associations, highlighting mosquitoes as dominant vectors and complex dual transmission dynamics for certain strains.