Indels and Host-Derived Sequences in Rat Hepatitis E Virus Genomes

Rat hepatitis E virus genotype 1 (rHEV) is an emerging zoonotic pathogen found globally in commensal rodents and is a significant cause of hepatitis, especially in immunocompromised populations. We systematically analyzed 99 rHEV genomes and identified multiple insertions and deletions predominantly within the macro X domain of ORF1, including a recurrent deletion of a 7−39 amino acid region in a large cluster of subtype II.b. Significant homology to human gene fragments was detected in 14% of genomes, including sequences related to transcription factors and phosphatases. This marks the first evidence of host genome-derived gene insertions in rHEV, expanding the understanding of rHEV genome plasticity, and highlights the need for further functional studies to elucidate the role of these variants in viral pathogenesis and zoonotic adaptation.