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PMID: 12915532 Published · ppublish English Journal Article

Respiratory syncytial virus infection sensitizes cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand.

Journal of virology ·Vol. 77 ·No. 17 ·2003-09-00 ·Pages 9156-72

Kotelkin A, Prikhod'ko EA, Cohen JI, Collins PL, Bukreyev A

Abstract

Respiratory syncytial virus (RSV) is an important cause of respiratory tract disease worldwide, especially in the pediatric population. For viruses in general, apoptotic death of infected cells is a mechanism for reducing virus replication. Apoptosis can also be an important factor in augmenting antigen presentation and the host immune response. We examined apoptosis in response to RSV infection of primary small airway cells, primary tracheal-bronchial cells, and A549 and HEp-2 cell lines. The primary cells and the A549 cell line gave generally similar responses, indicating their appropriateness as models in contrast to HEp-2 cells. With the use of RNase protection assays with probes representing 33 common apoptosis factors, we found strong transcriptional activation of both pro- and antiapoptotic factors in response to RSV infection, which were further studied at the protein level and by functional assays. In particular, RSV infection strongly up-regulated the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its functional receptors death receptor 4 (DR4) and DR5. Furthermore, RSV-infected cells became highly sensitive to apoptosis induced by exogenous TRAIL. These findings suggest that RSV-infected cells in vivo are susceptible to killing through the TRAIL pathway by immune cells such as natural killer and CD4(+) cells that bear membrane-bound TRAIL. RSV infection also induced several proapoptotic factors of the Bcl-2 family and caspases 3, 6, 7, 8, 9, and 10, representing both the death receptor- and mitochondrion-dependent apoptotic pathways. RSV also mediated the strong induction of antiapoptotic factors of the Bcl-2 family, especially Mcl-1, which might account for the delayed induction of apoptosis in RSV-infected cells in the absence of exogenous induction of the TRAIL pathway.

MeSH Terms
Apoptosis/physiology Apoptosis Regulatory Proteins Caspases/genetics,metabolism Cell Line Cells, Cultured Enzyme Activation Epithelial Cells/pathology,virology Humans Kinetics Lung/pathology,virology Membrane Glycoproteins/genetics,physiology Myeloid Cell Leukemia Sequence 1 Protein Neoplasm Proteins/genetics Proto-Oncogene Proteins c-bcl-2/genetics RNA, Messenger/genetics,metabolism Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor/genetics Respiratory Syncytial Virus Infections/etiology,genetics,pathology,virology Respiratory Syncytial Virus, Human/pathogenicity,physiology TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor-alpha/genetics,physiology Up-Regulation Virus Replication
Chemicals
Apoptosis Regulatory Proteins Membrane Glycoproteins Myeloid Cell Leukemia Sequence 1 Protein Neoplasm Proteins Proto-Oncogene Proteins c-bcl-2 RNA, Messenger Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor TNF-Related Apoptosis-Inducing Ligand TNFRSF10A protein, human TNFRSF10B protein, human TNFSF10 protein, human Tumor Necrosis Factor-alpha Caspases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kotelkin Alexander
Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Prikhod'ko Elena A
Cohen Jeffrey I
Collins Peter L
Bukreyev Alexander
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.17.9156-9172.2003
Published
2003-09-00
Pages
9156-72
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC187410
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.77.17.9156-9172.2003 PMC Full Text View journal details
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