Although MPXV M2 may affect both CD28- and CTLA4-mediated T cell activities via shared B7 molecules, we argue that MPXV M2 is likely to help the virus to antagonize host immune response due to the distinct expression patterns and levels of CD28 and CTLA4, especially at the early stage of viral infection when naïve T cell need to be primed to fight against invading pathogens. This evidence concerns the gene CD28 and viral infectious disease.