Staying undetected

Abstract

Downregulation of major histocompatibility complex (MHC) molecules is a well-recognized immune evasion mechanism used by several viruses. Cowpox virus (CPXV), for example, encodes the immune evasion protein CPXV203, which inhibits MHC class I trafficking by sequestering it in the endoplasmic reticulum (ER). However, CPXV203-deficient CPXV can still downregulate MHC class I surface expression, indicating that another mechanism must also be involved. Using distinct approaches, Byun et al. and Alzhanova et al. now show that the previously unknown cowpox protein CPXV12 mediates immune evasion by inhibiting effective MHC class I peptide biosynthesis.