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

Mohammad Jamaluddin, Shaofei Wang, Roberto P. Garofalo, Todd Elliott, Antonella Casola, Samuel Baron, Allan R. Brasier

Research output: Contribution to journalArticle

64 Scopus citations

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 infecious 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)-Β largely blocked TAP1/LMP2/LMP7 expression, whereas anti-interleukin-1 antibodies were without effect, and recombinant IFN-Β 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-Β to induce expression of the TAP1/LMP2/LMP7 locus, an event that may be important in the initiation of CTL-mediated lung injury.

Original languageEnglish (US)
Pages (from-to)L248-L257
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number2 24-2
StatePublished - Feb 1 2001

Keywords

  • 26S proteasome
  • ABC transporter
  • Interferon-β
  • Major histocompatibility complex class II locus
  • Pulmonary inflammation
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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