IFN-beta mediates coordinate expression of antigen-processing genes in RSV-infected pulmonary epithelial cells

Am J Physiol Lung Cell Mol Physiol. 2001 Feb;280(2):L248-57. doi: 10.1152/ajplung.2001.280.2.L248.

Abstract

Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) clear respiratory tract infections caused by the pneumovirus respiratory syncytial virus (RSV) and also mediate vaccine-induced pulmonary injury. Herein we examined the mechanism for RSV-induced MHC class I presentation. Like infectious viruses, conditioned medium from RSV-infected cells (RSV-CM) induces naive cells to coordinately express a gene cluster encoding the transporter associated with antigen presentation 1 (TAP1) and low molecular mass protein (LMP) 2 and LMP7. Neutralization of RSV-CM with antibodies to interferon (IFN)-beta largely blocked TAP1/LMP2/LMP7 expression, whereas anti-interleukin-1 antibodies were without effect, and recombinant IFN-beta increased TAP1/LMP2/LMP7 expression to levels produced by RSV-CM. LMP2, LMP7, and TAP1 expression were required for MHC class I upregulation because the irreversible proteasome inhibitor lactacystin or transfection with a competitive TAP1 inhibitor blocked inducible class I expression. We conclude that RSV infection coordinately increases MHC class I expression and proteasome activity through the paracrine action of IFN-beta to induce expression of the TAP1/LMP2/LMP7 locus, an event that may be important in the initiation of CTL-mediated lung injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / genetics
  • Antibodies / pharmacology
  • Antigen Presentation / drug effects
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • Cell Line
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology
  • Cysteine Endopeptidases*
  • Gene Expression Regulation / immunology*
  • Genes, MHC Class I / immunology
  • Genes, MHC Class II / immunology
  • Humans
  • Immediate-Early Proteins / metabolism
  • Immediate-Early Proteins / pharmacology
  • Interferon-beta / antagonists & inhibitors
  • Interferon-beta / immunology*
  • Interferon-beta / pharmacology
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / biosynthesis
  • Major Histocompatibility Complex / genetics
  • Major Histocompatibility Complex / immunology
  • Multienzyme Complexes*
  • Paracrine Communication / immunology
  • Peptide Hydrolases / drug effects
  • Peptide Hydrolases / metabolism
  • Proteasome Endopeptidase Complex*
  • Protein Biosynthesis
  • Proteins / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / virology
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Viruses / immunology
  • Respiratory Syncytial Viruses / metabolism
  • Viral Proteins*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Antibodies
  • Culture Media, Conditioned
  • ICP47 protein, Herpes simplex virus
  • Immediate-Early Proteins
  • Interleukin-1
  • Multienzyme Complexes
  • Proteins
  • RNA, Messenger
  • TAP1 protein, human
  • Viral Proteins
  • LMP-2 protein
  • Interferon-beta
  • Peptide Hydrolases
  • Cysteine Endopeptidases
  • LMP7 protein
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease