Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product.
Recognition of virus-infected cells by CD8+ cytotoxic T lymphocytes 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 histocompatibility complex class I molecule, and the antigenic complex exported to the cell surface. However, viral pathogens can disrupt this process and interfere with immune recognition. 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 expression. Products of CMV early-phase gene expression can globally block class I presentation 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 poorly. 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.
Gilbert
M J
MJ
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Riddell
S R
SR
Plachter
B
B
Greenberg
P D
PD
D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D005347:Fibroblasts; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000956:Antigens, Viral; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C044582:immediate-early proteins, cytomegalovirus