Varicella-Zoster Virus Activates CREB, and Inhibition of the pCREB-p300/CBP Interaction Inhibits Viral ReplicationIn Vitroand Skin PathogenesisIn Vivo Article Swipe
Sylvie François
,
Nandini Sen
,
Bryan Mitton
,
Xiangshu Xiao
,
Kathleen M. Sakamoto
,
Ann M. Arvin
·
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1128/jvi.00920-16
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1128/jvi.00920-16
Varicella-zoster virus (VZV) is an alphaherpesvirus that causes varicella upon primary infection and zoster upon reactivation from latency in sensory ganglion neurons. The replication of herpesviruses requires manipulation of cell signaling pathways. Notably, CREB, a factor involved in the regulation of several cellular processes, is activated upon infection of T cells with VZV. Here, we report that VZV infection also induced CREB phosphorylation in fibroblasts and that XX-650-23, a newly identified inhibitor of the phosphorylated-CREB (pCREB) interaction with p300/CBP, restricted cell-cell spread of VZV in vitro . CREB phosphorylation did not require the viral open reading frame 47 (ORF47) and ORF66 kinases encoded by VZV. Evaluating the biological relevance of these observations during VZV infection of human skin xenografts in the SCID mouse model of VZV pathogenesis showed both that pCREB was upregulated in infected skin and that treatment with XX-650-23 reduced infectious-virus production and limited lesion formation compared to treatment with a vehicle control. Thus, processes of CREB activation and p300/CBP binding are important for VZV skin infection and may be targeted for antiviral drug development. IMPORTANCE Varicella-zoster virus (VZV) is a common pathogen that causes chicken pox and shingles. As with all herpesviruses, the infection is acquired for life, and the virus can periodically reactivate from latency. Although VZV infection is usually benign with few or no deleterious consequences, infection can be life threatening in immunocompromised patients. Otherwise healthy elderly individuals who develop zoster as a consequence of viral reactivation are at risk for postherpetic neuralgia (PHN), a painful and long-lasting complication. Current vaccines use a live attenuated virus that is usually safe but cannot be given to many immunodeficient patients and retains the capacity to establish latency and reactivate, causing zoster. Antiviral drugs are effective against severe VZV infections but have little impact on PHN. A better understanding of virus-host cell interactions is relevant for developing improved therapies to safely interfere with cellular processes that are crucial for VZV pathogenesis.
Related Topics
Concepts
CREB
Varicella zoster virus
Biology
Virology
Shingles
Viral replication
Virus
Immunology
Chickenpox
Neurotropic virus
Pathogenesis
Viral entry
Virus latency
Transcription factor
Genetics
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1128/jvi.00920-16
- https://jvi.asm.org/content/jvi/90/19/8686.full.pdf
- OA Status
- bronze
- Cited By
- 13
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2496331681
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2496331681Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1128/jvi.00920-16Digital Object Identifier
- Title
-
Varicella-Zoster Virus Activates CREB, and Inhibition of the pCREB-p300/CBP Interaction Inhibits Viral ReplicationIn Vitroand Skin PathogenesisIn VivoWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2016Year of publication
- Publication date
-
2016-07-21Full publication date if available
- Authors
-
Sylvie François, Nandini Sen, Bryan Mitton, Xiangshu Xiao, Kathleen M. Sakamoto, Ann M. ArvinList of authors in order
- Landing page
-
https://doi.org/10.1128/jvi.00920-16Publisher landing page
- PDF URL
-
https://jvi.asm.org/content/jvi/90/19/8686.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://jvi.asm.org/content/jvi/90/19/8686.full.pdfDirect OA link when available
- Concepts
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CREB, Varicella zoster virus, Biology, Virology, Shingles, Viral replication, Virus, Immunology, Chickenpox, Neurotropic virus, Pathogenesis, Viral entry, Virus latency, Transcription factor, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
13Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 1, 2023: 1, 2022: 1, 2021: 2, 2020: 2Per-year citation counts (last 5 years)
- References (count)
-
51Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.interaction | 77 |
| abstract_inverted_index.reactivate, | 282 |
| abstract_inverted_index.replication | 24 |
| abstract_inverted_index.threatening | 226 |
| abstract_inverted_index.upregulated | 133 |
| abstract_inverted_index.development. | 177 |
| abstract_inverted_index.interactions | 305 |
| abstract_inverted_index.long-lasting | 253 |
| abstract_inverted_index.manipulation | 28 |
| abstract_inverted_index.observations | 112 |
| abstract_inverted_index.pathogenesis | 127 |
| abstract_inverted_index.periodically | 206 |
| abstract_inverted_index.postherpetic | 247 |
| abstract_inverted_index.reactivation | 16, 242 |
| abstract_inverted_index.complication. | 254 |
| abstract_inverted_index.consequences, | 221 |
| abstract_inverted_index.herpesviruses | 26 |
| abstract_inverted_index.pathogenesis. | 323 |
| abstract_inverted_index.understanding | 301 |
| abstract_inverted_index.herpesviruses, | 195 |
| abstract_inverted_index.immunodeficient | 272 |
| abstract_inverted_index.phosphorylation | 63, 89 |
| abstract_inverted_index.Varicella-zoster | 1, 179 |
| abstract_inverted_index.alphaherpesvirus | 6 |
| abstract_inverted_index.infectious-virus | 143 |
| abstract_inverted_index.immunocompromised | 228 |
| abstract_inverted_index.phosphorylated-CREB | 75 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 6 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7900000214576721 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.83117967 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |