Comparative Genomic Analysis of Two Bat Poxviruses in the Genus Vespertilionpoxvirus

Poxviruses are large double-stranded DNA (dsDNA) viruses that cause important human and animal diseases, including smallpox and mpox. Poxviruses have also been identified in diverse bat populations; however, their potential for zoonotic transmission and adaptation to other mammalian hosts remains poorly understood. Poxviruses encode numerous immunomodulatory proteins that contribute to virulence, immune evasion, and host range. In this study, we performed a comparative genomic analysis of two bat-associated poxviruses belonging to the genus Vespertilionpoxvirus: hypsugopox virus (HYPV) and eptesipox virus (EPTV). Our analyses revealed 24 novel putative ORFs in HYPV and three in EPTV, thereby substantially expanding the inferred coding capacity of these viruses. Comparative analyses further revealed gene duplication and fragmentation events affecting several virulence and host range factors, as well as other unusual genomic features, including the presence of two divergent E3L homologs in EPTV. Together, our findings provide new insights into the genome evolution and potential host adaptation of bat-associated poxviruses and establish a foundation for future functional studies of Vespertilionpoxvirus biology, host–virus interactions, and zoonotic potential.