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Cited by 66Respiratory viral infections researchNF-κB Signaling PathwaysRNA and protein synthesis mechanisms

Inducible translational regulation of the NF-IL6 transcription factor by respiratory syncytial virus infection in pulmonary epithelial cells

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Jamaluddin, M, Garofalo, R, Ogra, P L, Brasier, A R·1996·Journal of Virology
DOI 10.1128/jvi.70.3.1554-1563.1996PMC PMC189977
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Abstract

Respiratory syncytial virus (RSV), the most common etiologic agent of epidemic pediatric respiratory disease, infects and replicates in the human airway epithelium, resulting in the induction of cellular gene products essential for immune and inflammatory responses. We describe the effect of RSV infection on nuclear factor-IL6 (NF-IL6) expression, a human basic domain-leucine zipper-containing transcription factor that alone in combination with other inducible transcription factors regulates the expression of cytokine and adhesion molecule genes. RSV-infected human type II pulmonary alveolar epithelial cells (A549) synthesize a single 45.7-kDa isoform of NF-IL6 rapidly and in a time-dependent manner. NF-IL6 is first detectable after 3 h of infection and continues to accumulate until 48 h (until the cells lose viability). NF-IL6 production could not be induced by UV-inactivated virus, demonstrating the requirement of viral replication for NF-IL6 synthesis. Immunoprecipitation after [35S]methionine metabolic labeling was done to investigate the mechanism for NF-IL6 production. There was robust NF-IL6 protein synthesis within RSV-infected (24 h) cells. Protein synthesis occurred without detectable changes in the abundance or size of the single 1.8-kb NF-IL6 mRNA. RNase protection assay of transfected chloramphenicol acetyltransferase reporter genes driven by either wild-type or mutated NF-IL6 binding sites show a virus-induced increase in NF-IL6-dependent transcription. These studies have demonstrated a novel inducible mechanism for translational control of NF-IL6 synthesis and identify this transcription factor as a potential effector of the host response to RSV infection.

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Authors
Jamaluddin, M., Garofalo, R., Ogra, P. L., & Brasier, A. R.
Affiliations
The University of Texas Medical Branch at Galveston (US)
ORCID
Venue
Journal of Virology
Publisher
American Society for Microbiology
Published
1996-03
Volume
70
Issue
3
Pages
1554-1563
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
DOI
10.1128/jvi.70.3.1554-1563.1996
PMC
PMC189977
OpenAlex
W1780848409
Cited by
66
References
51
Citations by year
2023: 2 · 2021: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 1 · 2012: 1
FWCI
6.96
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Journal of Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (AI/HL 15939-14A1)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R30HD 27841)
Topics
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
respiratory syncytial virus, NF-IL6, C/EBP transcription factors, translational regulation, protein synthesis, alveolar epithelial cells, A549 cells, viral replication, host response to infection, transcriptional activation, cytokine gene expression, pediatric respiratory disease
MeSH terms
Base Sequence, Binding Sites, Cell Line, DNA, DNA-Binding Proteins, Epithelial Cells, Humans, Molecular Sequence Data, Nuclear Proteins, Oligodeoxyribonucleotides, Respiratory Syncytial Viruses, RNA, Messenger, Time Factors, Transcription Factors, Protein Biosynthesis, Virus Replication, CCAAT-Enhancer-Binding Proteins

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