Early growth response-1 protein is induced by JC virus infection and binds and regulates the JC virus promoter

Journal Article · Thu Jun 05 04:00:00 EDT 2008 · Virology

DOI:https://doi.org/10.1016/j.virol.2008.02.021· OSTI ID:21140994

Romagnoli, Luca; Sariyer, Ilker K; Tung, Jacqueline; Feliciano, Mariha; Sawaya, Bassel E; Del Valle, Luis ^[1]; Ferrante, Pasquale ^[2]; Khalili, Kamel; Safak, Mahmut ^[1]

---

1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122 (United States)
2. Laboratorio Analisi, San Giuseppe Hospital, Via San Vittore, 12, 20123 Milan (Italy)

JC virus (JCV) is a human polyomavirus that can emerge from a latent state to cause the cytolytic destruction of oligodendrocytes in the brain resulting in the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Previous studies described a cis-acting transcriptional regulatory element in the JCV non-coding control region (NCCR) that is involved in the response of JCV to cytokines. This consists of a 23 base pair GGA/C rich sequence (GRS) near the replication origin (5112 to + 4) that contains potential binding sites for Sp1 and Egr-1. Gel shift analysis showed that Egr-1, but not Sp1, bound to GRS. Evidence is presented that the GRS gel shift seen on cellular stimulation is due to Egr-1. Thus, TPA-induced GRS gel shift could be blocked by antibody to Egr-1. Further, the TPA-induced GRS DNA/protein complex was isolated and found to contain Egr-1 by Western blot. No other Egr-1 sites were found in the JCV NCCR. Functionally, Egr-1 was found to stimulate transcription of JCV late promoter but not early promoter reporter constructs. Mutation of the Egr-1 site abrogated Egr-1 binding and virus with the mutated Egr-1 site showed markedly reduced VP1 expression and DNA replication. Infection of primary astrocytes by wild-type JCV induced Egr-1 nuclear expression that was maximal at 5-10 days post-infection. Finally, upregulation of Egr-1 was detected in PML by immunohistochemistry. These data suggest that Egr-1 induction may be important in the life cycle of JCV and PML pathogenesis.

• OSTI ID: 21140994
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 375; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
BRAIN
DNA
DNA REPLICATION
GELS
LIFE CYCLE
LYMPHOKINES
PATHOGENESIS
PROMOTERS
STIMULATION
TRANSCRIPTION
VIRUSES