Processing and presentation of murine cytomegalovirus pORFm164-derived peptide in fibroblasts in the face of all viral immunosubversive early gene functions

J Virol. 2002 Jun;76(12):6044-53. doi: 10.1128/jvi.76.12.6044-6053.2002.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, Viral* / genetics
  • Antigens, Viral* / immunology
  • Cells, Cultured
  • Female
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Genes, Immediate-Early / genetics
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / immunology
  • Immediate-Early Proteins / metabolism
  • Membrane Glycoproteins* / chemistry
  • Membrane Glycoproteins* / genetics
  • Membrane Glycoproteins* / immunology
  • Mice
  • Mice, Inbred BALB C
  • Muromegalovirus / chemistry
  • Muromegalovirus / immunology*
  • Open Reading Frames / genetics
  • Peptide Fragments* / chemistry
  • Peptide Fragments* / genetics
  • Peptide Fragments* / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Proteins*

Substances

  • Antigens, Viral
  • IE1 protein, cytomegalovirus
  • Immediate-Early Proteins
  • Membrane Glycoproteins
  • Peptide Fragments
  • Viral Proteins
  • immediate-early proteins, cytomegalovirus