Virus-Triggered ATP Release Limits Viral Replication through Facilitating IFN-β Production in a P2X7-Dependent Manner
Abstract
Accumulating evidence shows that innate immune responses are associated with extracellular nucleotides, particularly ATP. In this article, we demonstrate extensive protection of ATP/P2X7 signaling in a host against viral infection. Interestingly, we observed a significant increase in ATP as a danger signal in vesicular stomatitis virus (VSV)-infected cell supernatant and VSV-infected mice in an exocytosis- and pannexin channel–dependent manner. Furthermore, extracellular ATP reduces the replication of VSV, Newcastle disease virus, murine leukemia virus, and HSV in vivo and in vitro through the P2X7 receptor. Meanwhile, ATP significantly increases IFN-β expression in a concentration- and time-dependent manner. Mechanistically, ATP facilitates IFN-β secretion through P38/JNK/ATF-2 signaling pathways, which are crucial in promoting antiviral immunity. Taken together, these results demonstrate the protective role of extracellular ATP and P2X7 in viral infection and suggest a potential therapeutic role for ATP/P2X7 in viral diseases.
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The P2X7 receptor participates in viral infections, exerting mostly pro-inflammatory roles, is important for pathogen elimination, but its activation may be detrimental to the host due to induction of exacerbated inflammatory responses.
“The P2X7 receptor, as a central player in inflammation, participates in viral infections. Exerting mostly pro-inflammatory roles [20], the P2X7 receptor is important for pathogen elimination [108], but on the other hand, its activation may be detrimental to the host due to the induction of exacerbated inflammatory responses.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [108]
Protective roles of P2X7 receptor activation have been described against vesicular stomatitis virus, Newcastle disease virus, murine leukemia virus and HSV virus infections.
“Protective roles of P2X7 receptor activation have been described, for instance, against vesicular stomatitis virus, Newcastle disease virus, murine leukemia virus and HSV virus infections [108].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [108]
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- Authors
- Zhang, C., He, H., Wang, L., Zhang, N., Huang, H., Xiong, Q., Yan, Y., Wu, N., Ren, H., Han, H., Liu, M., Qian, M., & Du, B.
- Affiliations
- East China Normal University (CN)
- Biomarker Technologies (China) (CN)
- Corresponding author
- Zhang, Chengfei
- He, Hongwang
- Wang, Li
- Zhang, Na
- Huang, Hongjun
- Xiong, Qingqing
- Yan, Yan
- Wu, Nannan
- Ren, Hua
- Liu, Mingyao
- Qian, Min
- Du, Bing
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-08
- Volume
- 199
- Issue
- 4
- Pages
- 1372-1381
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2732208398
- Cited by
- 76
- References
- 33
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 14 · 2021: 13 · 2020: 19 · 2019: 7 · 2018: 5
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- extracellular ATP, P2X7 receptor, vesicular stomatitis virus, interferon-beta, antiviral innate immunity, pannexin channels, exocytosis, viral replication, Newcastle disease virus, murine leukemia virus, herpes simplex virus, damage-associated molecular patterns
- MeSH terms
- RAW 264.7 Cells, Adenosine Triphosphate, Animals, Immunity, Innate, Luminescent Measurements, Leukemia Virus, Murine, Newcastle disease virus, Vesicular stomatitis Indiana virus, Virus Replication, Signal Transduction, Interferon-beta, Simplexvirus, Mice, Vesicular Stomatitis, Receptors, Purinergic P2X7
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