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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.
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Research Article Virology

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

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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

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Figure 1

HSV-1 infection increases Egr-1 expression.

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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.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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