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

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

Research output: Contribution to journalArticle

64 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number2 24-2
StatePublished - Feb 2001

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Respiratory Syncytial Viruses
Antigen Presentation
Interferons
Epithelial Cells
Major Histocompatibility Complex
Lung
Genes
Lung Injury
Cytotoxic T-Lymphocytes
Pneumovirus
Respiratory Syncytial Virus Infections
Proteasome Inhibitors
Antibodies
Proteasome Endopeptidase Complex
Multigene Family
Conditioned Culture Medium
Interleukin-1
Respiratory Tract Infections
Transfection
Up-Regulation

Keywords

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

ASJC Scopus subject areas

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

Cite this

IFN-β mediates coordinate expression of antigen-processing genes in RSV-infected pulmonary epithelial cells. / Jamaluddin, Mohammad; Wang, Shaofei; Garofalo, Roberto; Elliott, Todd; Casola, Antonella; Baron, Samuel; Brasier, Allan R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 280, No. 2 24-2, 02.2001.

Research output: Contribution to journalArticle

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