The lumpy skin disease virus protein LSDV003 regulates MHC-I trafficking and surface expression.

LSDV003 from lumpy skin disease virus markedly downregulates MHC-I surface expression in infected host cells, with ER retention driven by a C-terminal HNEL motif.

• Why it matters: Cytotoxic T-cell control is critical in poxvirus infections, but LSDV immune-evasion strategies targeting MHC-I trafficking are poorly understood.
• What they did: The study screened LSDV-encoded proteins, then showed LSDV003 interacts with the MHC-I heavy chain and β2-microglobulin and mediates ER retention via the HNEL motif; HNEL disruption impaired MHC-I relocalization and surface expression.
• The result: An LSDV003-deficient virus exhibited a markedly reduced capacity to suppress MHC-I surface expression during infection, identifying LSDV003 as a regulator of MHC-I trafficking and immune recognition.