IFN-ß 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, and Allan R. Brasier.
Departments of 1Medicine and 4Sealy Center for Molecular Science, 2Pediatrics and
3Microbiology and Immunology, The University of Texas Medical Branch, Galveston,
Texas 77555«hyphen»1060
APStracts 7:0254L, 2000.
Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes
(CTL) 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 naïve cells to
coordinately express a gene cluster encoding the transporter-associated antigen
presentation 1 (TAP1) and low molecular mass proteins (LMP)2 and LMP7.
Neutralization of RSV-CM with antibodies to interferon (IFN)-ß largely blocked
TAP1/LMP2/LMP7 expression, whereas anti-interleukin-1 antibodies were without
effect, and recombinant IFN-ß 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-ß to induce expression of the
TAP1/LMP2/LMP7 locus, an event that may be important in the initiation of CTL-
mediated lung injury.
Received 26 April 2000; accepted in final form 7 September 2000
APS Manuscript Number L138-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 7 November 2000