Regulation of Human Neurotropic JC Virus Replication by Alternative Splicing Factor SF2/ASF in Glial Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Feb 8

PMID 21297941

Citations 21

Authors

Ilker Kudret Sariyer

Kamel Khalili

Affiliations

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Abstract

Background: The human neurotropic virus, JC virus (JCV), is the etiologic agent of the fatal demyelinating disease of the central nervous system, Progressive Multifocal Leukoencephalopathy (PML) that is seen primarily in immunodeficient individuals. Productive infection of JCV occurs only in glial cells, and this restriction is, to a great extent, due to the activation of the viral promoter that has cell type-specific characteristics. Earlier studies led to the hypothesis that glial-specific activation of the JCV promoter is mediated through positive and negative transcription factors that control reactivation of the JCV genome under normal physiological conditions and suppress its activation in non-glial cells.

Methodology/principal Findings: Using a variety of virological and molecular biological approaches, we demonstrate that the alternative splicing factor SF2/ASF has the capacity to exert a negative effect on transcription of the JCV promoter in glial cells through direct association with a specific DNA sequence within the viral enhancer/promoter region. Our results show that down-regulation of SF2/ASF in fetal and adult glial cells increases the level of JCV gene expression and its replication indicating that negative regulation of the JCV promoter by SF2/ASF may control reactivation of JCV replication in brain.

Conclusions/significance: Our results establish a new regulatory role for SF2/ASF in controlling gene expression at the transcriptional level.

Citing Articles

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The oncogenic roles of JC polyomavirus in cancer.

Zheng H, Xue H, Zhang C Front Oncol. 2022; 12:976577.

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Determining host factors contributing to the reactivation of JC virus in kidney transplant recipients.

Keykhosravi S, Khosravi M, Shenagari M, Hasan-Alizadeh E, Mosadegh M, Noori Goodarzi N Virol J. 2022; 19(1):131.

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JCPyV NCCR analysis in PML patients with different risk factors: exploring common rearrangements as essential changes for neuropathogenesis.

Ciardi M, Zingaropoli M, Iannetta M, Prezioso C, Perri V, Pasculli P Virol J. 2020; 17(1):23.

PMID: 32046748 PMC: 7014659. DOI: 10.1186/s12985-020-1295-5.

Host-Immune Interactions in JC Virus Reactivation and Development of Progressive Multifocal Leukoencephalopathy (PML).

Khalili A, Craigie M, Donadoni M, Sariyer I J Neuroimmune Pharmacol. 2019; 14(4):649-660.

PMID: 31452013 PMC: 6898772. DOI: 10.1007/s11481-019-09877-8.

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