Abstract
RECOGNITION of virus-infected cells by CD8+ cytotoxic T lympho-cytes requires that the viral proteins be processed into peptides, the derived peptides transported into the endoplasmic reticulum and inserted into the binding groove of a major histocompatability complex class I molecule, and the antigenic complex exported to the cell surface1. However, viral pathogens can disrupt this process and interfere with immune recognition1–4. These mechanisms may be vital to large viruses such as human cytomegalovirus (CMV), which causes persistent infection despite producing over 200 potentially antigenic proteins during the sequential immediate–early, early and late phases of viral gene expression5,6. Products of CMV early-phase gene expression can globally block class I presentation7–10 and prevent recognition of infected cells by cytotoxic T lymphocytes, but an essential viral transcription factor, the 72K principal immediate–early protein, is abundantly expressed before this blockade. However, only a few host CD8+ cytotoxic T lymphocytes specific for immediate–early protein are present in seropositive individuals, and these lyse CMV-infected cells poorly11. Here we demonstrate selective abrogation of immediate–early peptide presentation by a CMV matrix protein with associated kinase activity and suggest that modification of a viral protein can result in limiting access to the processing machinery and evasion of cytotoxic-T-cell recognition.
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Gilbert, M., Riddell, S., Plachter, B. et al. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate–early gene product. Nature 383, 720–722 (1996). https://doi.org/10.1038/383720a0
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DOI: https://doi.org/10.1038/383720a0
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