Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Suppression of transcription factor early growth response 1 reduces herpes simplex virus lethality in mice
Shih-Heng Chen, … , Ching Li, Shun-Hua Chen
Shih-Heng Chen, … , Ching Li, Shun-Hua Chen
Published September 2, 2008
Citation Information: J Clin Invest. 2008;118(10):3470-3477. https://doi.org/10.1172/JCI35114.
View: Text | PDF
Research Article Virology

Suppression of transcription factor early growth response 1 reduces herpes simplex virus lethality in mice

  • Text
  • PDF
Abstract

Herpes simplex virus type 1 (HSV-1) infection is the most common cause of sporadic, fatal encephalitis, but current understanding of how the virus interacts with cellular factors to regulate disease progression is limited. Here, we show that HSV-1 infection induced the expression of the cellular transcription factor early growth response 1 (Egr-1) in a human neuronal cell line. Egr-1 increased viral replication by activating promoters of viral productive cycle genes through binding to its corresponding sequences in the viral promoters. Mouse studies confirmed that Egr-1 expression was enhanced in HSV-1–infected brains and that Egr-1 functions to promote viral replication in embryonic fibroblasts. Furthermore, Egr-1 deficiency or knockdown of Egr-1 by a DNA-based enzyme greatly reduced the mortality of HSV-1–infected mice by decreasing viral loads in tissues. This study provides what we believe is the first evidence that Egr-1 increases the mortality of HSV-1 encephalitis by enhancing viral replication. Moreover, blocking this cellular machinery exploited by the virus could prevent host mortality.

Authors

Shih-Heng Chen, Hui-Wen Yao, I-Te Chen, Biehuoy Shieh, Ching Li, Shun-Hua Chen

×

Figure 1

HSV-1 infection increases Egr-1 expression.

Options: View larger image (or click on image) Download as PowerPoint
HSV-1 infection increases Egr-1 expression.
The viral growth (A) and Egr...
The viral growth (A) and Egr-1 expression assayed by RT-PCR (B) and Western blot (C) analyses were monitored in SK-N-SH cells infected with strain KOS or with UV-inactivated virus (UV). M, molecular weight marker. (D) The brain stem regions of Egr-1+/+ and Egr-1–/– C57BL/6 mice mock infected or infected with strain 294.1 were harvested at day 6 p.i. and stained with DAPI or antibodies against Egr-1 or viral antigen glycoprotein D (gD). Original magnification, ×200. Data are representative of at least 2 experiments.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts