Recently Added Frameshift Mutation in Human Monkeypox Virus (hMPXV) OPG191 Gene.

Abstract

Human monkeypox virus (hMPXV) has caused sporadic outbreaks intermittently across countries in recent years, with the largest outbreak in 2022. However, the underlying mechanisms remain unclear. This study searched for recently developed structural variants of the viral genome. A total of 22 hMPXV whole genome sequences were randomly selected from the National Center for Biotechnology Information GenBank sequence database for initial screening. As a result, a recent frameshift mutation based on a 2-base insertion in a coding region was identified at the 3' terminal of the OPG191 gene, which encodes MPXVgp168 (B7R) protein. With this insertion, the protein was prematurely truncated, and the last 11 amino acids were missing, with 3 alternative amino acids added. Among the hMPXV genome sequences registered in the GenBank database as of January 2023, 61 sequences lacked the 2-base insertion and 3,362 sequences were inserted. All 61 sequences without mutations were collected before 2020, whereas 3,358 (99.9%) of the 3,362 sequences with the insertion were collected during or after 2022. These findings imply that a 2-base insertion has recently emerged and has been fixed among the virus population that prevailed in 2022. In summary, a recently emerged frameshift mutation with a 2-base insertion was identified in hMPXV OPG191 gene. Although the structural and functional consequences of this mutation on virulence and infectivity are unknown, research on the possible associations between this mutation and recent hMPXV outbreaks is warranted.