Selective mechanisms utilized by persistent and oncogenic viruses to interfere with antigen processing and presentation

Abstract

Cell-mediated immunity is effective against cells harboring active virus replication, and is critical for the elimination of ongoing infections, regression of virus-associated tumors, and reducing or preventing the reactivation of persistent viruses. The capacity of persistent and oncogenic viruses to maintain a long-term relationship with their host presupposes viral mechanisms for circumventing antiviral defenses. By suppressing the expression of molecules associated with antigen processing and presentation, viruses abrogate the major immune mechanism that deals with the elimination of infected and tumor cells. This is accomplished either by transcriptional downregulation of genes encoding class I MHC antigens, peptide transporter molecules, and the proteasome-associated LMP subunits, or by interfering with transport of class I molecules to the cell surface. In some cases viruses shut off the expression of most viral proteins during latency or express mainly nonimmunogenic or antagonistic peptide epitopes. This review describes selective mechanisms utilized by viruses for interference with antigen processing and presentation, and addresses their significance for in vivo viral persistence and tumor progression.

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

“…Many viral pathogens have evolved mechanisms to down-regulate MHC class I presentation of viral Ags. Some produce mimic FcRs and others alter cytokine profiles (1)(2)(3). A few viruses elaborate T cell superantigens (SAgs) 3 that expand T cell subpopulations independent of virus specificity that can result in cytokine shock and cause clonal deletion (4,5).…”

Synthesis and Turnover of β2-Microglobulin in Ad12-transformed Cells Defective in Assembly and Transport of Class I Major Histocompatibility Complex Molecules

“…This mechanism enables the immune system to control infectious diseases and the growth of tumor cells (2,3). Indeed, cells infected by a variety of viruses that interfere with cell surface expression of class I antigens, as well as tumors of various origins that demonstrate suppressed levels of class I antigens, can escape immune surveillance (4).…”

“…The trimeric complex is then transported through the Golgi apparatus to the cell surface. Mutant cell lines (5)(6)(7)(8), "knockout" mice (9,10), and tumor cells (4,11,12), which do not express TAP genes, are generally devoid of cell surface MHC class I molecules. Cell lines and knockout mice lacking ␤ 2 m expression also fail to display normal cell surface class I MHC molecules (13)(14)(15).…”

MHC Class I Heavy Chain mRNA Must Exceed a Threshold Level for the Reconstitution of Cell Surface Expression of Class I MHC Complexes in Cells Transformed by the Highly Oncogenic Adenovirus 12

“…This mechanism enables the immune system to control infectious diseases and the growth of tumor cells (2)(3)(4).…”

“…Mutant cell lines (5,6,10,11), "knockout" mice (12,13), and tumor cells (4,14,15), which do not express TAP genes and/or ␤ 2 m (16 -18), are generally devoid of cell surface MHC class I molecules. We have previously shown that in cell lines derived from primary embryonal fibroblasts from transgenic mice expressing both the endogenous H-2 genes and a miniature swine class I transgene (PD1), transformation with the highly oncogenic Ad12 results in a significant reduction in peptide transporter (TAP1 and TAP2) and in proteasome-associated (LMP2 and LMP7) gene expression, and consequently in suppression of cell surface expression of all class I antigens (15, 19 -21).…”