Processing and presentation of murine cytomegalovirus pORFm164-derived peptide in fibroblasts in the face of all viral immunosubversive early gene functions.
CD8 T cells are the principal effector cells in the resolution of acute murine cytomegalovirus (mCMV) infection in host organs. This undoubted antiviral and protective in vivo function of CD8 T cells appeared to be inconsistent with immunosubversive strategies of the virus effected by early (E)-phase genes m04, m06, and m152. The so-called immune evasion proteins gp34, gp48, and gp37/40, respectively, were found to interfere with peptide presentation at different steps in the major histocompatibility complex (MHC) class I pathway of antigen processing and presentation in fibroblasts. Accordingly, they were proposed to prevent recognition and lysis of infected fibroblasts by cytolytic T lymphocytes (CTL) during the E phase of viral gene expression. We document here that the previously identified MHC class I D(d)-restricted antigenic peptide (257)AGPPRYSRI(265) encoded by gene m164 is processed as well as presented for recognition by m164-specific CTL during the E and late phases of viral replication in the very same cells in which the immunosubversive viral proteins are effectual in preventing the presentation of processed immediate-early 1 (m123-exon 4) peptide (168)YPHFMPTNL(176). Thus, while immunosubversion is a reality, these mechanisms are apparently not as efficient as the term immune evasion implies. The pORFm164-derived peptide is the first noted peptide that constitutively escapes the immunosubversive viral functions. The most important consequence is that even the concerted action of all immunosubversive E-phase proteins eventually fails to prevent immune recognition in the E phase. The bottom-line message is that there exists no immune evasion of mCMV in fibroblasts.
Holtappels
Rafaela
R
Institute for Virology, Johannes Gutenberg University, 55101 Mainz, Germany.
Grzimek
Natascha K A
NK
Simon
Christian O
CO
Thomas
Doris
D
Dreis
Doris
D
Reddehase
Matthias J
MJ
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D017781:Genes, Immediate-Early / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000737:chemistry / Q000276:immunology*; D016366:Open Reading Frames / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014764:Viral Proteins
D000956:Antigens, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C044582:immediate-early proteins, cytomegalovirus