Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Mediate Inhibition of Stat2 Expression and Alpha/Beta Interferon Responsiveness
Open accessAbstract
Respiratory syncytial virus (RSV) subverts the antiviral interferon (IFN) response, but the mechanism for this evasion was unclear. Here we show that RSV preferentially inhibits IFN-α/β signaling by expression of viral NS1 and NS2. Thus, RSV infection or expression of recombinant NS1 and NS2 in epithelial host cells causes a marked decrease in Stat2 levels and the consequent downstream IFN-α/β response. Similarly, NS1/NS2-deficient RSV no longer decreases Stat2 levels or IFN responsiveness. RSV infection decreased human but not mouse Stat2 levels, so this mechanism of IFN antagonism may contribute to viral host range, as well as immune subversion.
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Parainfluenza viruses inhibit IRF-3 activation.
“IRF-3 activation is inhibited by RSV (273) and parainfluenza viruses (165).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [165]
Parainfluenza viruses target the phosphorylation of IRF3 specifically, by encoding V accessory proteins which act as substrates for the kinases TBK1 and IKK-ι/ɛ.
“In contrast, parainfluenza viruses target the phosphorylation of IRF3 specifically, by encoding V accessory proteins which act as substrates for the kinases TBK1 and IKK-ι/ɛ.”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [165]
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- Authors
- Lo, M. S., Brazas, R. M., & Holtzman, M. J.
- Affiliations
- Departments of Medicine
- Duke Medical Center (US)
- Washington University in St. Louis (US)
- Corresponding author
- Holtzman, Michael J.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2005-07
- Volume
- 79
- Issue
- 14
- Pages
- 9315-9319
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC1168759
- OpenAlex
- W2051874642
- Cited by
- 284
- References
- 26
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 9 · 2020: 20 · 2019: 13 · 2018: 7 · 2017: 12 · 2016: 12 · 2015: 16 · 2014: 17 · 2013: 11 · 2012: 14
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- respiratory syncytial virus, NS1 protein, NS2, STAT2, interferon-alpha/beta signaling, interferon antagonism, viral immune evasion, host range, epithelial cells, antiviral response
- MeSH terms
- Cell Line, DNA-Binding Proteins, Humans, Signal Transduction, Trans-Activators, Interferon-alpha, Interferon-beta, Viral Nonstructural Proteins, Respiratory Syncytial Virus, Human, Respiratory Syncytial Virus Infections, STAT2 Transcription Factor
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