Cytomegalovirus selectively blocks antigen processing and presentation of its immediate–early gene product
- 24 October 1996
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 383 (6602), 720-722
- https://doi.org/10.1038/383720a0
Abstract
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.Keywords
This publication has 37 references indexed in Scilit:
- The Human Cytomegalovirus US11 Gene Product Dislocates MHC Class I Heavy Chains from the Endoplasmic Reticulum to the CytosolCell, 1996
- A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytesCell, 1994
- Identification of the major late human cytomegalovirus matrix protein pp65 as a target antigen for CD8+ virus‐specific cytotoxic T lymphocytesJournal of Medical Virology, 1994
- Peptides Naturally Presented by MHC Class I MoleculesAnnual Review of Immunology, 1993
- Virus proteins that counteract host immune defensesCell, 1992
- Antigen presentation in virus infectionCurrent Opinion in Immunology, 1992
- Modulation of MHC antigen expression by viruses and oncogenesImmunology Today, 1991
- Genomic location of a human cytomegalovirus protein with protein kinase activity (PK68)Virology, 1990
- Human Cytomegalovirus: Recent Aspects from Molecular BiologyJournal of General Virology, 1989
- The Two Major Structural Phosphoproteins (pp65 and pp150) of Human Cytomegalovirus and Their Antigenic PropertiesJournal of General Virology, 1987