Molecular epidemiology and phylogeny of the emerging zoonotic virus Rocahepevirus: A global genetic analysis

Human infections with Rocahepevirus ratti genotype C1 (HEV-C1) in Hong Kong of China, Canada, Spain, and France have drawn worldwide concern towards Rocahepevirus. This study conducted a global genetic analysis of Rocahepevirus, aiming to furnish comprehensive molecular insights and promote further research. We retrieved 817 Rocahepevirus sequences from the GenBank database through October 31, 2023, categorizing them according to research, sample collection area and date, genotype, host, and sequence length. Subsequently, we conducted descriptive epidemiological, phylogenetic evolutionary, and protein polymorphism (in length and identity) analyses on these sequences. Rocahepevirus genomes were identified across twenty-eight countries, predominantly in Asia (71.73%, 586/817) and Europe (26.44%, 216/817). The HEV-C1 dominates Rocahepevirus (77.2%, 631/817), while newly discovered Rocahepevirus genotypes (C3/C4/C5 and other unclassified genotypes) were primarily identified in Europe (25/120) and China (91/120). Muridae animals (72.5%, 592/817) serve as the primary hosts for Rocahepevirus, with other hosts encompassing species from the families Soricidae, Hominidae, Mustelidae, and Cricetidae. Additionally, Rocahepevirus genomes (C1 genotype) were identified in sewage samples recently. The phylogenetic evolution of Rocahepevirus exhibits considerable variation. Specifically, HEV-C1 can be classified into at least six genetic groups (G1 to G6), with human HEV-C1 distributed across multiple evolutionary clades. The overall ORF1 and ORF2 amino acid sequence lengths were significantly different (P < 0.001) across Rocahepevirus genotypes. HEV-C1/C2/C3 and HEV-C4/C5 displayed substantial differences in amino acid sequence identity (58.4%-59.6%). The identification of Rocahepevirus genomes has expanded across numerous countries, particularly in European and Asian countries, coinciding with an expanding host range and emergence of new genotypes. The evolutionary path of Rocahepevirus is intricate, where the HEV-C1 dominates globally and internally forms multiple evolutionary groups (G1 to G6), exhibiting diverse genetic variation within human HEV-C1. Significant differences exist in the protein polymorphism (in length and identity) across Rocahepevirus genotypes. Given Rocahepevirus's shift from an animal virus to a zoonotic pathogen, worldwide cooperation in monitoring Rocahepevirus genomes is vital.