Cell cycle arrest in G2/M phase enhances replication of interferon-sensitive cytoplasmic RNA viruses via inhibition of antiviral gene expression

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Grdzelishvili, V., Bressy, C., Droby, G. N., Maldonado, B. D., & Steuerwald, N. (2019). Cell cycle arrest in G2/M phase enhances replication of interferon-sensitive cytoplasmic RNA viruses via inhibition of antiviral gene expression. Journal Of Virology. https://doi.org/doi:10.1128/JVI.01885-18
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Description

Vesicular stomatitis virus (VSV) (a rhabdovirus) and its variant VSV-ΔM51 are widely used model systems to study mechanisms of virus-host interactions. Here, we investigated how the cell cycle affects replication of these viruses using an array of cell lines with different levels of impairment of antiviral signaling and a panel of chemical compounds arresting the cell cycle at different phases. We observed that all compounds inducing cell cycle arrest in G2/M phase strongly enhanced the replication of VSV-ΔM51 in cells with functional antiviral signaling. G2/M arrest strongly inhibited type I and type III interferon (IFN) production as well as expression of IFN-stimulated genes in response to exogenously added IFN. Moreover, G2/M arrest enhanced the replication of Sendai virus (a paramyxovirus), which is also highly sensitive to the type I IFN response but did not stimulate the replication of a wild-type VSV that is more effective at evading antiviral responses. In contrast, the positive effect of G2/M arrest on virus replication was not observed in cells defective in IFN signaling. Altogether, our data show that replication of IFN-sensitive cytoplasmic viruses can be strongly stimulated during G2/M phase as a result of inhibition of antiviral gene expression, likely due to mitotic inhibition of transcription, a global repression of cellular transcription during G2/M phase. The G2/M phase thus could represent an "Achilles' heel" of the infected cell, a phase when the cell is inadequately protected. This model could explain at least one of the reasons why many viruses have been shown to induce G2/M arrest.

Details
Title

Cell cycle arrest in G2/M phase enhances replication of interferon-sensitive cytoplasmic RNA viruses via inhibition of antiviral gene expression

Author(s)

Grdzelishvili, Valery
Bressy, Christian
Droby, Gaith N.
Maldonado, Bryant D.
Steuerwald, Nury

UNC Charlotte Affiliate Type

Faculty

Publisher

American Society for Microbiology

Extent

1 online resource

Date Published

2019

Material Type

Journal article

Genre

articles

Resource Type

text

Abstract

Vesicular stomatitis virus (VSV) (a rhabdovirus) and its variant VSV-ΔM51 are widely used model systems to study mechanisms of virus-host interactions. Here, we investigated how the cell cycle affects replication of these viruses using an array of cell lines with different levels of impairment of antiviral signaling and a panel of chemical compounds arresting the cell cycle at different phases. We observed that all compounds inducing cell cycle arrest in G2/M phase strongly enhanced the replication of VSV-ΔM51 in cells with functional antiviral signaling. G2/M arrest strongly inhibited type I and type III interferon (IFN) production as well as expression of IFN-stimulated genes in response to exogenously added IFN. Moreover, G2/M arrest enhanced the replication of Sendai virus (a paramyxovirus), which is also highly sensitive to the type I IFN response but did not stimulate the replication of a wild-type VSV that is more effective at evading antiviral responses. In contrast, the positive effect of G2/M arrest on virus replication was not observed in cells defective in IFN signaling. Altogether, our data show that replication of IFN-sensitive cytoplasmic viruses can be strongly stimulated during G2/M phase as a result of inhibition of antiviral gene expression, likely due to mitotic inhibition of transcription, a global repression of cellular transcription during G2/M phase. The G2/M phase thus could represent an "Achilles' heel" of the infected cell, a phase when the cell is inadequately protected. This model could explain at least one of the reasons why many viruses have been shown to induce G2/M arrest.

Subjects--Topics

Cancer
Viruses

Is Part Of

Journal of virology

Volume

Vol. 93, issue 4

Language

English

Published Version (Please cite this version)

doi:10.1128/JVI.01885-18

Publisher's Version

https://doi.org/10.1128/JVI.01885-18

Permalink

http://hdl.handle.net/20.500.13093/work:212

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