Skip to content
Research Article Open access CC BY 3.0

Induction of Transcription Factor Early Growth Response Protein 1 during HSV-1 Infection Promotes Viral Replication in Corneal Cells

S. C. Hsia, L. P. Graham, G. R. Bedadala, M. B. Balish, F. Chen, R. W. Figliozzi

Microbiology Research Journal International · pp. 706–723 · Published 3 Sep 2013

10.9734/BMRJ/2013/4817

Abstract

Aims: To understand the mechanisms of Early Growth Response Protein 1 (Egr-1) induction upon HSV-1 lytic infection and its roles in regulating viral gene expression and replication. Study Design: Rabbit corneal cell line SIRC and other cell lines were infected by HSV-1 to investigate the Egr-1 induction and its occupancy on the viral genome in different conditions. UV-inactivated HSV-1 and a recombinant virus over-expressing Egr-1 were generated to evaluate the regulatory effects on viral gene expression and replication during the infection. Methodology: Egr-1 induction triggered by viral infection was determined by Western Blot analyses and immune-fluorescent microscopy. Real-time RT-PCR and a novel Cignal™ Reporter Assay were used for quantitative measurement of Egr-1 expression. Chromatin Immuno-precipitation (ChIP) was performed to address the Egr-1 occupancy to the viral regulatory sequences and the influence on viral replication was assessed by plaque assays. Results: Our results indicated that Egr-1 expression requires viral gene expression since the UV-inactivated HSV-1 failed to produce Egr-1 protein. Blockade of viral replication did not block the Egr-1 protein synthesis, supporting the hypothesis that HSV-1 replication was not essential for Egr-1 production. Chromatin immune-precipitation (ChIP) and RT-PCR assays demonstrated that induced Egr-1 was able to interact with key regulatory elements near HSV-1 immediate-early (IE) genes and promote viral gene expression. Recombinant virus overexpressing Egr-1 revealed that Egr-1 enhanced the viral replication and the release of infectious virus. Conclusion: Together these results concluded that HSV-1 triggers the expression of an important host transcription factor Egr-1 via a unique mechanism and benefit the viral gene expression and replication.

Egr-1 HSV-1 lytic infection viral replication corneal cells.

References (32)

  1. 1 Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases [DOI]
  2. 2 A Nerve Growth Factor-Induced Gene Encodes a Possible Transcriptional Regulatory Factor [DOI]
  3. 3 Regulation of life and death by the zinc finger transcription factor Egr‐1 [DOI]
  4. 4 Egr transcription factors in the nervous system [DOI]
  5. 5 Extracellular Signal-Regulated Kinase (ERK) Controls Immediate Early Gene Induction on Corticostriatal Stimulation [DOI]
  6. 6 DNA-Binding Specificity of NGFI-A and Related Zinc Finger Transcription Factors [DOI]
  7. 7 Coactivating Factors p300 and CBP Are Transcriptionally Crossregulated by Egr1 in Prostate Cells, Leading to Divergent Responses [DOI]
  8. 8 Characterization of nerve growth factor-dependent herpes simplex virus latency in neurons in vitro [DOI]
  9. 9 Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro [DOI]
  10. 10 Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency [DOI]
  11. 11 Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses [DOI]
  12. 12 p300-Dependent ATF5 Acetylation Is Essential for Egr-1 Gene Activation and Cell Proliferation and Survival [DOI]
  13. 13 A Novel Repression Module, an Extensive Activation Domain, and a Bipartite Nuclear Localization Signal Defined in the Immediate-Early Transcription Factor Egr-1 [DOI]
  14. 14 Nab1, a Corepressor of NGFI-A (Egr-1), Contains an Active Transcriptional Repression Domain [DOI]
  15. 15 Egr1 Signaling in Prostate Cancer [DOI]
  16. 16 Stability and circularization of herpes simplex virus type 1 genomes in quiescently infected PC12 cultures [DOI]
  17. 17 Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1) in rabbit corneal cells [DOI]
  18. 18 Effects of thyroid hormone on HSV-1 gene regulation: implications in the control of viral latency and reactivation [DOI]
  19. 19 Induction of cellular transcription factors in trigeminal ganglia of mice by corneal scarification, herpes simplex virus type 1 infection, and explantation of trigeminal ganglia [DOI]
  20. 20 Expression of the enhanced green fluorescent protein by herpes simplex virus type 1 (HSV-1) as an in vitro or in vivo marker for virus entry and replication [DOI]
  21. 21 Early Growth Response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression [DOI]
  22. 22 Long term herpes simplex virus type 1 infection of nerve growth factor-treated PC12 cells [DOI]
  23. 23 Suppression of Transcription Factor Early Growth Response 1 Reduces Herpes Simplex Virus 1-Induced Corneal Disease in Mice [DOI]
  24. 24 The HSV 1 genome in quiescently infected NGF differentiated PC12 cells can not be stimulated by HSV superinfection [DOI]
  25. 25 Early and Delayed Shut-off of Host Protein Synthesis in Cells Infected with Herpes Simplex Virus [DOI]
  26. 26 Nerve growth factor induces expression of immediate-early genes NGFI-A (Egr-1) and NGFI-B (nur 77) in adult rat dorsal root ganglion neurons [DOI]
  27. 27 Nerve Growth Factor Induces zif288 Gene Expression via MAPK-Dependent and -Independent Pathways in PC12D Cells [DOI]
  28. 28 Repression of the HSV-1 latency-associated transcript (LAT) promoter by the early growth response (EGR) proteins: Involvement of a binding site immediately downstream of the TATA box [DOI]
  29. 29 Suppression of transcription factor early growth response 1 reduces herpes simplex virus lethality in mice [DOI]
  30. 30 Co-factors p300 and CBP catch egr1 in their network [DOI]
  31. 31 Antiviral activity and synthesis of quaternized promazine derivatives against HSV-1 [DOI]
  32. 32 J. Virol. Methods [DOI]

Cited by 30

EGR Proteins Mediate Interferon‐Independent Anti‐HSV‐1 Responses Through Viral and Host Targets

Shuaishuai Wang, Fujun Hou, Xunuo Jin · Advancement of science · 2026

Egr-1 is a key regulator of the blood-brain barrier damage induced by meningitic Escherichia coli

Rui-Cheng Yang, Xin-Yi Wang, Hulin Liu · Cell Communication and Signaling · 2024

Examining the role of EGR1 during viral infections

Caitlin M. Woodson, K. Kehn-Hall · Frontiers in Microbiology · 2022

Speckles and paraspeckles coordinate to regulate HSV-1 genes transcription

Kun Li, Zi-Qiang Wang · Communications Biology · 2021

The Yin and Yang of YY1 in tumor growth and suppression

L. Khachigian · International Journal of Cancer · 2018

Showing 26 of 30 known citations — external sources report more than can currently be individually listed.

Article metrics

Real usage data collected on this platform.

69

Page views

0

PDF downloads

8

Outbound clicks

30

Citations

Views over time

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

Traffic sources

Referring site, by host.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.