Genomic analysis identifies unreported adaptive mutations in monkeypox virus immune evasion genes.

Mpox virus (MPXV) is a zoonotic Orthopoxvirus that has recently gained attention due to outbreaks. In the presence of these constantly changing global health threats, genomic surveillance of the MPXV is no longer a choice but a necessity. The MPXV has diversified through mutation and adaptation, giving rise to distinct clades. In this study, the Nextclade tool was used to identify amino acid substitutions in immune evasion genes relative to the reference genome NC_063383.1 across the African, European, and Asian continents. Crm-B secreted TNF-alpha receptor-like protein, Bcl-2-like protein, and B22R Serpin are key immune evasion proteins, exhibited a high prevalence of mutations. Phylogenetic analysis of lineage-specific mutations was performed on genes encoding immune evasion proteins, such as OPG002, OPG176, and OPG210. CGView analysis revealed different genomic structures for these genes, whereas InterProScan identified important functional domains associated with immune modulation. The sets provide important clues into the mutational landscape of the MPXV, underscoring the crucial need for continued monitoring of viral adaptation and the emergence of new variants. These mutations have not been reported previously in this dataset of 40 sequences. However, confirming their global frequency needs larger genomic MPXV datasets, studies, and experimental testing. These findings are based on a hypothesis and are specific to functional and genomic scrutiny.