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

Alexander Kotelkin, Elena A. Prikhod'ko, Jeffrey I. Cohen, Peter L. Collins, Alexander Bukreyev

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)9156-9172
Number of pages17
JournalJournal of Virology
Volume77
Issue number17
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

Respiratory Syncytial Virus Infections
tumor necrosis factors
Respiratory Syncytial Viruses
apoptosis
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
viruses
infection
cells
Caspase 6
TNF-Related Apoptosis-Inducing Ligand Receptors
Respiratory Tract Diseases
Death Domain Receptors
Antigen Presentation
Ribonucleases
Virus Replication
cell lines
ligands
Caspase 3

ASJC Scopus subject areas

  • Immunology

Cite this

Respiratory syncytial virus infection sensitizes cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand. / Kotelkin, Alexander; Prikhod'ko, Elena A.; Cohen, Jeffrey I.; Collins, Peter L.; Bukreyev, Alexander.

In: Journal of Virology, Vol. 77, No. 17, 01.09.2003, p. 9156-9172.

Research output: Contribution to journalArticle

Kotelkin, Alexander ; Prikhod'ko, Elena A. ; Cohen, Jeffrey I. ; Collins, Peter L. ; Bukreyev, Alexander. / Respiratory syncytial virus infection sensitizes cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand. In: Journal of Virology. 2003 ; Vol. 77, No. 17. pp. 9156-9172.
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